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Context Sepsis-induced acute lung injury (ALI) is a severe condition with limited effective therapeutics; nicotinamide mononucleotide (NMN) has been reported to exert anti-inflammatory activities.Objective This study explores the potential mechanisms by which NMN ameliorates sepsis-induced ALI in vivo and in vitro.Materials and methods Cultured MH-S cells and a murine model were used to evaluate the effect of NMN on sepsis-induced ALI. MH-S cells were stimulated with LPS (1 μg/mL) and NMN (500 μM) for 12 h grouping as control, LPS, and LPS + NMN. Cell viability, apoptotic status, and M1/2 macrophage-related markers were detected. The mice were pretreated intraperitoneally with NMN (500 mg/kg) and/or EX-527 (5 mg/kg) 1 h before LPS injection and randomized into 7 groups (n = 8): control, LPS, LPS + NMN, NMN, LPS + NMN + EX-527 (a SIRT1 inhibitor), LPS + EX-527, and EX-527. After 12 h, lung histopathology, W/D ratio, MPO activity, NAD+ and ATP levels, M1/2 macrophage-related markers, and expression of the SIRT1/NF-κB pathway were detected.Results In MH-S cells, NMN significantly decreased the apoptotic rate from 12.25% to 5.74%. In septic mice, NMN improved the typical pathologic findings in lungs and reduced W/D ratio and MPO activity, but increased NAD+ and ATP levels. Additionally, NMN suppressed M1 but promoted M2 polarization, and upregulated the expression of SIRT1, with inhibition of NF-κB-p65 acetylation and phosphorylation. Furthermore, inhibition of SIRT1 reversed the effects of NMN-induced M2 macrophage polarization.Conclusions NMN protects against sepsis-induced ALI by promoting M2 macrophage polarization via the SIRT1/NF-κB pathway, it might be an effective strategy for preventing or treating sepsis-induced ALI.

Abstract Locomotor preferences and habitat types may drive animal evolution. In this study, we speculated that locomotor preference and habitat type may have diverse influences on Bovidae mitochondrial genes. We used selection pressure and statistical analysis to explore the evolution of mitochondrial DNA (mtDNA) protein-coding genes (PCGs) from diverse locomotor preferences and habitat types. Our study demonstrates that locomotor preference (energy demand) drives the evolution of Bovidae in mtDNA PCGs. The habitat types had no significant effect on the rate of evolution in Bovidae mitochondrial genes. Our study provides deep insight into the adaptation of Bovidae.

Abstract Several studies have investigated the gut bacterial composition of wild ungulates in the Qinghai–Xizang Plateau. However, the relationship between their gut microbiome dendrograms and their phylogenetic tree remains unclear. In this study, we analyzed 45 amplicons (V3–V4 region of the 16S rRNA gene) from five wild ungulates—Pseudois nayaur, Pantholops hodgsonii, Gazella subgutturosa, Bos grunniens, and Equus kiang—from the Qinghai–Xizang Plateau to clarify the relationship between their phylogenies and gut microbiome dendrograms. The unweighted pair group method with arithmetic mean analysis and hierarchical clustering analysis indicated that G. subgutturosa is closely related to P. nayaur; however, these results were inconsistent with their phylogenetic trees. Additionally, the indicator genera in the microbiome of each wild ungulate showed strong associations with the diets and habitats of their host. Thus, diet and space niche differentiation may primarily account for the differences between the gut microbiome characteristics of these wild ungulates and their phylogeny. In summary, our research provides insights into the evolutionary factors influencing the gut microbiome of wild ungulates in the Qinghai–Xizang Plateau.

Abstract We obtain three‐dimensional models of crustal shear‐wave velocity and radial anisotropy in the Bohai Bay basin (BBB), revealing distinct radial anisotropy patterns. The western region of the basin exhibits pronounced positive crustal radial anisotropies, attributed to upper mantle convection driven by the subduction of the Pacific plate during the early Tertiary. Conversely, the eastern region of the basin demonstrates weak to negative radial anisotropies, indicating a compression shear rupture system influenced by the far‐field India‐Eurasian collision during the Neogene‐Quaternary. These differences suggest that the formation of the BBB is associated with the dynamic transition from Pacific subduction to India‐Eurasian collision during the Cenozoic. Moreover, the Luxi uplift, with its stable upper‐middle crustal structures, acts as a barrier hindering the eastward extension of the BBB.

ABSTRACTMicroorganisms are a crucial component of lake ecosystems and significant contributors to biogeochemical cycles. However, the understanding of how primary microorganism groups (e.g., bacteria and fungi) are distributed and constructed within different lake habitats is lacking. We investigated the bacterial and fungal communities of Hulun Lake using high-throughput sequencing techniques targeting 16S rRNA and Internal Transcribed Spacer 2 genes, including a range of ecological and statistical methodologies. Our findings reveal that environmental factors have high spatial and temporal variability. The composition and community structures vary significantly depending on differences in habitats. Variance partitioning analysis showed that environmental and geographical factors accounted for

Single-cell RNA sequencing (scRNA-seq) is now a successful technology for identifying cell heterogeneity, revealing new cell subpopulations, and predicting developmental trajectories. A crucial component in scRNA-seq is the precise identification of cell subsets. Although many unsupervised clustering methods have been developed for clustering cell subpopulations, the performance of these methods is prone to be affected by dropout, high dimensionality, and technical noise. Additionally, most existing methods are time-consuming and fail to fully consider the potential correlations between cells. In this paper, we propose a novel unsupervised clustering method called scVGATAE (Single-cell Variational Graph Attention Autoencoder) for scRNA-seq data. This method constructs a reliable cell graph through network denoising, utilizes a novel variational graph autoencoder model integrated with graph attention networks to aggregate neighbor information and learn the distribution of the low-dimensional representations of cells, and adaptively determines the model training iterations for various datasets. Finally, the obtained low-dimensional representations of cells are clustered using kmeans. Experiments on nine public datasets show that scVGATAE outperforms classical and state-of-the-art clustering methods.

Abstract Pre-harvest sprouting (PHS) is one of the major threats to global food security as it significantly affects cereals’ production and quality. PHS tolerance depends on diverse factors, among which phytohormones and germination-inhibitory substances (GISs) play essential roles. However, in wheat, information related to GIS in the glume is scarce. Thus, we applied LC–MS/MS-based metabolomics analysis to explore the polyphenols and phytohormones profiles of two contrasting wheat genotypes, Lincang Hulled Wheat (LHW, PHS-resistant) and Yunmai53 (Yun53, PHS-highly susceptible). Physiological tests revealed that LHW PHS-resistance is not associated with the ability of its spikelet to prevent water absorption. The total polyphenol content of the spikes and shells of LHW was significantly higher than that of Yun53, respectively. In total, 214 phenolic compounds classified mainly into phenolic acids (42.52%), flavones (23.83%), and flavonoid carbonosides (16.36%) were identified. 180 differentially accumulated polyphenols (DAPs) were uncovered, including 168 up-regulated in LHW. 24 most up-regulated DAPs (Log2FC ≥ 8) were unveiled as potential candidate GISs. Of the identified phytohormones, abscisic acid, salicylic acid, and jasmonic acid exhibited significantly higher content in LHW compared to Yun53. Whereas, Yun53 contained significantly higher levels of ethylene and gibberellin than LHW. Our findings offer new resources for PHS control in wheat.

Abstract Background and aim Immunohistochemistry indicators are increasingly being used to predict the survival prognosis of cancer patients after surgery. This study aimed to combine some markers to establish an immunohistochemical score (MSI-P53-Ki-67[MPK]) and stratify postoperative patients with gastric cancer according to the score. Methods We used 245 patients who underwent surgery at one center as the training cohort and 111 patients from another center as the validation cohort. All patients were treated between January 2012 and June 2018. The training cohort was screened for prognostic factors, and MPK scores were established using univariate and multifactorial COX risk proportional models. Patients were prognostically stratified according to the MPK score after gastrectomy for gastric cancer. Overall survival (OS) and recurrence-free survival (RFS) rates were compared among low-, intermediate-, and high-risk groups using the Kaplan–Meier method, and survival curves were plotted. Finally, the MPK score was validated using the validation cohort. Results In the training group, there were statistically significant differences in OS and RFS in the low, medium, and high-risk groups (P

Body size may drive the molecular evolution of mitochondrial genes in response to changes in energy requirements across species of different sizes. In this study, we perform selection pressure analysis and phylogenetic independent contrasts (PIC) to investigate the association between molecular evolution of mitochondrial genome protein-coding genes (mtDNA PCGs) and body size in terrestrial Cetartiodactyla. Employing selection pressure analysis, we observe that the average non-synonymous/synonymous substitution rate ratio (ω) of mtDNA PCGs is significantly reduced in small-bodied species relative to their medium and large counterparts. PIC analysis further confirms that ω values are positively correlated with body size (R2 = 0.162, p = 0.0016). Our results suggest that mtDNA PCGs of small-bodied species experience much stronger purifying selection as they need to maintain a heightened metabolic rate. On the other hand, larger-bodied species may face less stringent selective pressures on their mtDNA PCGs, potentially due to reduced relative energy expenditure per unit mass. Furthermore, we identify several genes that undergo positive selection, possibly linked to species adaptation to specific environments. Therefore, despite purifying selection being the predominant force in the evolution of mtDNA PCGs, positive selection can also occur during the process of adaptive evolution.

Various active solar heating systems have been developed to enhance the Chinese assembled solar greenhouse winter cultivation capacity by using renewable energy rather than traditional fossil fuel resources. These systems involve an efficient heat-collecting and transfer pattern, which solar energy can be converted into heat energy and flexibly utilized according to heating requirements, without unwarranted heating. To improve CASG thermal performance in high latitudes and cold regions, we modified the water-circulating solar heat collection and release system. The new structure was able to collect the solar radiation on the sheet during daytime to further generate heat through the magnetron sputtering plate. The collector also functions as a heating radiator during nighttime to protect crops from chilling injury in frigid weather. Field tests and economical analysis were performed to investigate the system’s thermal and energy-saving performance by analyzing several core parameters. Test results indicated that the average daily heat collection ratio of the system was 70.2%. The minimum nighttime indoor air temperature heated by the system was increased by 3.5 °C on average and maintained the temperatures above 9 °C after 2–3 cloudy days. The mean COP in heat collection and release phase were 8.2 and 2.4 over a period of 7 test days, respectively. The energy saving efficiency of the system was 44.1%. The novel system proposed in this study using thermal insulation structure and reasonable mass area ratio enables higher heat storage capacity and structure practicability. We demonstrated that the novel technology proposed in this study displayed energy saving characteristics. The new active solar heating system can be effectively used in high latitudes Chinese assembled solar greenhouse winter cultivation.

Hydraulic fracture modelling is a key component of a shale reservoir well placement strategy as it provides an indication of the typical lengths and heights of stimulated fractures and of the changes to the stress environment in which these are propagating. However, spatial and stratigraphic variations in the stress and geomechanical properties of shales make accurate modelling a challenging task. For the UK Bowland Shale, stacked horizontal wells targeting multiple stratigraphic intervals could be used to avoid large offset faults in a geologically complex area. However, it is not known how these intervals may respond to hydraulic fracturing and predicting the height and length of hydraulic fractures is necessary in order to assess the likelihood of vertical fracture interference across landing zones or propagation towards major faults. In the case of the former, intervals of high effective stress may be key to containing fractures within their desired target. Using a planar hydraulic fracture simulator, and a 3D geomechanical model incorporating dipping stratigraphy, the issue of predicting hydraulic fracture geometry in the Bowland Shale was assessed through a series of modelling exercises using well Preese Hall-1 and horizontal pseudo-wells. When pre-defined landing zones were targeted, narrow and long transverse fractures around 1 km from the well were simulated. When the simulation design mimicked perforation clusters placed at 12 m intervals along horizontal pseudo-wells, the effects of stress shadowing were acute and resulted in irregular fracture geometries. Furthermore, high effective stress intervals performed efficiently as barriers to vertical hydraulic fracture propagation, reinforcing the feasibility of using stacked production for the Bowland Shale. The modelling results were then used to discuss the possible placement of horizontal wells in a mapped, 100 km2 region around well Preese Hall-1, where up to 13 sites could be positioned, with a horizontal well length of around 1.5 km. Finally, by drawing on a well-established analogue for the Bowland Shale, it was estimated that up to 195 Bcf of gas could be produced from the 13 locations in the area if three stratigraphic intervals are produced from one location.

Abstract Background After surgery, millions of people suffer from delayed healing or wound dehiscence with subsequent severe complications, even death. Previous studies have reported that ropivacaine exhibits anti-proliferative and anti-migratory activities on numerous cells. Whether ropivacaine is able to influence the proliferation and migration of keratinocytes is still unclear. This study aimed to investigate the effect of ropivacaine on keratinocytes and its underlying molecular mechanism. Methods Adult male Sprague–Dawley rats were allocated to establish wound healing models with or without 0.75% ropivacaine treatment and assessed the epidermal thickness by HE staining. HaCaT cells were cultured to evaluate the effect of ropivacaine on wound healing. The cell proliferation, apoptosis status and migration were detected in vitro. Moreover, western blotting was used to examine expression to with PI3K/AKT/mTOR signaling pathways for molecular studies and the changes in inflammatory factors (IL-6, IL-10, TNF-α) were detected by ELISA. Results In the present study, we found that ropivacaine delayed wound closure in vivo. In vitro experiments, it was demonstrated that ropivacaine significantly inhibited the proliferation and migration of HaCaT cells via the suppression of PI3K/AKT/mTOR signaling pathway. Activation of PI3K/AKT/mTOR signaling pathway reversed the effects of ropivacaine on the proliferation and migration of HaCaT cells. Furthermore, ropivacaine contributed to the release of pro-inflammatory cytokines (IL-6 and TNF-α) and inhibited the secretion of anti-inflammatory cytokines of keratinocytes (IL-10). Conclusions Our research demonstrated that ropivacaine treatment showed a more decreased wound closure rate. Mechanistically, we found that ropivacaine suppressed the proliferation and migration of keratinocytes and altered the expression of cytokines by inhibiting PI3K/AKT/mTOR pathway.

Using premier Language Environment Analysis technology to measure and analyze the home language environment, this observational study aims to describe the home language environment and child language ability, drawing on empirical data from 77 households with children aged 18–24 months from rural China. The results show large variation in measures of the home language environment and early language ability, similar to other rural Chinese samples. Results also demonstrate significant correlations between child age and the home language environment, maternal employment and the home language environment, father’s educational attainment and the home language environment, adult–child conversations and early language ability, and child vocalizations and early language ability.

Abstract Continuous monitoring of glucose allows diabetic patients to better maintain blood glucose level by altering insulin dosage or diet according to prevailing glucose values and thus to prevent potential hyperglycemia and hypoglycemia. However, current continuous glucose monitoring (CGM) relies mostly on enzyme electrodes or micro‐dialysis probes, which suffer from insufficient stability, susceptibility to corrosion of electrodes, weak or inconsistent correlation, and inevitable interference. A fluorescence‐based glucose sensor in the skin will likely be more stable, have improved sensitivity, and can resolve the issues of electrochemical interference from the tissue. This study develops a fluorescent nanodiamond boronic hydrogel system in porous microneedles for CGM. Fluorescent nanodiamond is one of the most photostable fluorophores with superior biocompatibility. When surface functionalized, the fluorescent nanodiamond can integrate with boronic polymer and form a hydrogel, which can produce fluorescent signals in response to environmental glucose concentration. In this proof‐of‐concept study, the strategy for building a miniatured device with fluorescent nanodiamond hydrogel is developed. The device demonstrates remarkable long‐term photo and signal stability in vivo with both small and large animal models. This study presents a new strategy of fluorescence based CGM toward treatment and control of diabetes.