Search

Abstract Chlorophyll a (Chl-a) is a key indicator of marine ecosystems, and certain hydro-meteorological parameters (HMPs) are highly correlated with its fluctuations. Here, relevant and accessible HMPs were used as inputs, combined with machine learning (ML) algorithms for estimating 3D Chl-a in the South China Sea (SCS). With the inputs of temperature, salinity, depth, wind speed, wind direction, sea surface pressure, and relative humidity, the LightGBM-based model performed well, achieving high R2 values of 0.985 and 0.789 in validation and testing sets, respectively. Based on a large number of in situ measurements, this model enables the estimation of the 3D distribution of summer Chl-a in the SCS over the past fifteen years using a 3D hydrographic dataset combined with surface meteorological parameters. The results show that the 3D distribution of the model estimated Chl-a is characterized similarly to the previous studies and can capture the effect of hydro-meteorological conditions on Chl-a distribution. The environmental variables affecting Chl-a were considered more comprehensively in this study, and the methodological framework has the potential to be applied to the low-cost monitoring of the remaining water quality parameters.

Intracellular delivery of biologicals such as peptides, proteins, and nucleic acids presents a great opportunity for innovative therapeutics. However, the endosome entrapment remains a major bottleneck in the intracellular delivery of biomacromolecules, largely limiting their therapeutic potential. Here, we converted a cell-penetrating peptide (CPP), low molecular weight protamine (LMWP), to endosomal escape peptides (EEPs) by masking LMWP with a pH-responsive counter-ionic peptide. The resulting masked CPPs (mLMWP and mLMWP2) effectively promoted the escape of peptide/protein cargoes from endosomes into the cytoplasm. Consequential lysosome repair and lysophagy were initiated upon the endolysosomal leakage. Minimal reactive oxygen species (ROS) elevation or cell death was observed. Based on mLMWP2, we constructed an intracellular protein delivery system containing an antibody as a targeting module, mLMWP2 as an endosomal escape module, and the desired protein cargo. With the HER2-targeting delivery system, we efficiently translocated cyclization recombination enzyme (Cre) and BH3-interacting domain death agonist (BID) into the cytosol of HER2+ cells to exert their biological activity. Thereby, the modular delivery system shows its potential as a promising tool for scientific studies and therapeutic applications.

Abstract Background Lung cancer is one of the major threats to human life worldwide. MiR‐190 has been found to perform essential roles in multiple cancer progression; however, there have been no studies focused on its function and underlying regulatory mechanism in lung cancer. Method The miR‐190 expression was detected by real‐time quantitative polymerase chain reaction (RT‐qPCR). The cell functional experiments, including cell counting kit‐8 (CCK‐8), colony formation and transwell assay were conducted in vitro, as well as animal experiments performed in vivo. The regulation and potential binding sites of CBX4 on miR‐190 were predicted by TCGA data set and JASPAR website and verified by ChIP assay and dual‐luciferase reporter assay. The prospects binding site of miR‐190‐3p on CBX4 3′UTR region was predicted by StarBase and verified by dual‐luciferase reporter assay. Results MiR‐190 was decreased in lung cancer cells. The overexpression of miR‐190 had no effects on cell proliferation, but significantly inhibited cancer metastasis both in vitro and in vivo. Moreover, miR‐190 expression could be transcriptionally inhibited by CBX4, and CBX4 was the direct target of miR‐190‐3p. Conclusion MiR‐190 served as a cancer metastasis inhibitor in lung cancer and formed a regulatory loop with CBX4. These findings provided emerging insights into therapeutic targets and strategies for metastatic lung cancer.

Abstract Tropical cyclone activity often leads to many adverse impacts and assessing their destructiveness is a crucial scientific concern. Here we investigated changes in the destructiveness of tropical cyclones worldwide using the power dissipation index and found that there is no clear trend in most basins, but a significant decrease in power dissipation index has been detected in the South Indian Ocean basin since 1994, which is almost entirely due to a decrease in both tropical cyclone frequency and duration in this basin. The decrease in tropical cyclone frequency is influenced by increased atmospheric stability. The decrease in tropical cyclone duration can be attributed to the changes in tropical cyclone locations. In addition, the weakened subtropical high is only observed in the South Indian Ocean (i.e., the Mascarene High), which is also associated with the decrease in tropical cyclone destructiveness. These findings have implications for assessing the destructive potential of future tropical cyclones.

Introduction Vaccination against SARS-CoV-2 is an integral pillar of the public health approach to COVID-19. With the emergence of variants of concern that increase transmissibility and escape from vaccine- or infection-induced protection, vaccines have been developed to more closely match the newly circulating SARS-CoV-2 strains to improve protection. The safety and immunogenicity of multiple authorized messenger RNA (mRNA)-based COVID-19 vaccines targeting the omicron sublineage (BA.1, BA.4/BA.5, and XBB.1.5) have been demonstrated in several clinical trials among adults and children.Areas covered This review will comprehensively detail the available evidence (published through July 2024) from ongoing clinical trials on omicron variant-containing mRNA-1273 vaccines administered as additional doses in previously vaccinated target demographics.Expert opinion Across three clinical trials, omicron variant-containing mRNA-1273 vaccines induced immune responses to vaccine-matched omicron strains as well as ancestral SARS-CoV-2, with a safety and reactogenicity profile comparable to the original mRNA-1273 vaccine. Combined with pivotal data demonstrating the safety, efficacy, and effectiveness of the original mRNA-1273 vaccine, these findings support the use of variant-containing mRNA-1273 vaccines and provide confidence that expeditious development of updated vaccines using this established mRNA platform can maintain protection against COVID-19.

Abstract Immune checkpoint inhibitors (ICIs) have achieved remarkable success in clinical research and practice. Notably, liver metastasis is not sensitive to ICIs. Liver locoregional therapies can cause irreversible damage to tumor cells and release tumor antigens, thereby providing a rationale for immunotherapy treatments in liver metastasis. The combination therapy of ICIs with locoregional therapies is a promising option for patients with liver metastasis. Preclinical studies have demonstrated that combining ICIs with locoregional therapies produces a significantly synergistic anti-tumor effect. However, the current evidence for the efficacy of ICIs combined with locoregional therapies remains insufficient. Therefore, we review the literature on the mechanisms of locoregional therapies in treating liver metastasis and the clinical research progress of their combination with ICIs.

Abstract Individuals’ continuous success in competitive interactions with conspecifics strongly affects their social hierarchy. Medial prefrontal cortex (mPFC) is the key brain region mediating both social competition and hierarchy. However, the molecular regulatory mechanisms underlying the neural ensemble in the mPFC remains unclear. Here, we demonstrate that in excitatory neurons of prelimbic cortex (PL), lncRNA Sera remodels the utilization of Pkm Exon9 and Exon10, resulting in a decrease in the Pkm1/2 ratio in highly competitive mice. By employing a tet-on/off system, we disrupt or rebuild the normal Pkm1/2 ratio by controlling the expression of Pkm2 in PL excitatory neurons. We find that long-term Pkm2 modulation induces timely competition alteration and hysteretic rank change, through phosphorylating the Ser845 site of GluA1. Together, this study uncovers a crucial role of lncRNA Sera/Pkm2 pathway in the transition of social competition to rank by remodeling neural ensemble in mPFC.

Abstract Blood vessels are highly dynamic and complex structures with a variety of physiological functions, including the transport of oxygen, nutrients, and metabolic wastes. Their normal functioning involves the close and coordinated cooperation of a variety of cells. However, adverse internal and external environmental factors can lead to vascular damage and the induction of various vascular diseases, including atherosclerosis and thrombosis. This can have serious consequences for patients, and there is an urgent need for innovative techniques to repair damaged blood vessels. Polyesters have been extensively researched and used in the treatment of vascular disease and repair of blood vessels due to their excellent mechanical properties, adjustable biodegradation time, and excellent biocompatibility. Given the high complexity of vascular tissues, it is still challenging to optimize the utilization of polyesters for repairing damaged blood vessels. Nevertheless, they have considerable potential for vascular tissue engineering in a range of applications. This summary reviews the physicochemical properties of polyhydroxyalkanoate (PHA), polycaprolactone (PCL), poly-lactic acid (PLA), and poly(lactide-co-glycolide) (PLGA), focusing on their unique applications in vascular tissue engineering. Polyesters can be prepared not only as 3D scaffolds to repair damage as an alternative to vascular grafts, but also in various forms such as microspheres, fibrous membranes, and nanoparticles to deliver drugs or bioactive ingredients to damaged vessels. Finally, it is anticipated that further developments in polyesters will occur in the near future, with the potential to facilitate the wider application of these materials in vascular tissue engineering.

AIM: To analyze the changes in scientific output relating to Leber congenital amaurosis (LCA) and forecast the study trends in this field. METHODS: All of the publications in the field of LCA from 2002 to 2022 were collected from Web of Science (WOS) database. We analyzed the quantity (number of publications), quality (citation and H-index) and development trends (relative research interest, RRI) of published LCA research over the last two decades. Moreover, VOSviewer software was applied to define the co-occurrence network of keywords in this field. RESULTS: A total of 2158 publications were ultimately examined. We found that the focus on LCA kept rising and peaked in 2015 and 2018, which is consistent with the development trend of gene therapy. The USA has contributed most to this field with 1162 publications, 56 674 citations and the highest H-index value (116). The keywords analysis was divided into five clusters to show the hotspots in the field of LCA, namely mechanism-related, genotype-related, local phenotype-related, system phenotype-related, and therapy-related. We also identified gene therapy and anti-retinal degeneration therapy as a major focus in recent years. CONCLUSION: Our study illustrates historical research process and future development trends in LCA field. This may help to guide the orientation for further clinical diagnosis, treatment and scientific research.

Abstract Analyzing the genetic diversity and selection characteristics of sheep (Ovis aries) holds significant value in understanding their environmental adaptability, enhancing breeding efficiency, and achieving effective conservation and rational utilization of genetic resources. In this study, we utilized Illumina Ovine SNP 50 K BeadChip data from four indigenous sheep breeds from the southern margin of the Taklamakan Desert (Duolang sheep: n = 36, Hetian sheep: n = 74, Kunlun sheep: n = 27, Qira black sheep: n = 178) and three foreign meat sheep breeds (Poll Dorset sheep: n = 105, Suffolk sheep: n = 153, Texel sheep: n = 150) to investigate the population structure, genetic diversity, and genomic signals of positive selection within the indigenous sheep. According to the Principal component analysis (PCA), the Neighbor-Joining tree (NJ tree), and Admixture, we revealed distinct clustering patterns of these seven sheep breeds based on their geographical distribution. Then used Cross Population Extended Haplotype Homozygosity (XP-EHH), Fixation Index (FST), and Integrated Haplotype Score (iHS), we identified a collective set of 32 overlapping genes under positive selection across four indigenous sheep breeds. These genes are associated with wool follicle development and wool traits, desert environmental adaptability, disease resistance, reproduction, and high-altitude adaptability. This study reveals the population structure and genomic selection characteristics in the extreme desert environments of native sheep breeds from the southern edge of the Taklimakan Desert, providing new insights into the conservation and sustainable use of indigenous sheep genetic resources in extreme environments. Additionally, these findings offer valuable genetic resources for sheep and other mammals to adapt to global climate change.

Abstract Tropical cyclones (TCs) have experienced poleward migration in recent years, but whether this exists in future projections with high-resolution climate models remains unclear. This study investigates the poleward migration of TCs over the western North Pacific (WNP) using CMIP6-HighResMIP models. We first assess the model performance in TC genesis frequency and latitude, which differ greatly from the observations, especially in winter and spring due to misinterpretation of extratropical storms. In this study, we put forward a revised constrained detection method based on the sea surface temperature (SST) and the atmospheric conditions to resolve this bias. Results indicate that the revised detection method has good performance in capturing the annual cycle of TC genesis frequency and latitude. Future projections constrained by this method show that the latitude of TC genesis and lifetime maximum intensity (LMI) both undergo a poleward shift, with the former being more significant. Spatial changes in the dynamic potential genesis index and large-scale environment could explain this shift. The regional changes of Hadley circulation and the role of global warming and internal variability are also discussed.

Abstract The main part of oil‐immersed power equipment is oil‐paper insulation. At lower ambient temperatures, transformer oil will become viscous. As a result, compared to those at room temperature or operating temperature, the frequency domain dielectric properties of oil‐paper insulation at low temperatures are drastically different. For evaluating the insulation condition of electrical equipment, it is essential to accurately determine their dielectric properties. This paper described the FDS test, the DC conductivity test, and the transformer oil viscosity test, which was carried out in a laboratory environment for different ageing of oil‐immersed pressboard and transformer oil at 233–373 K. The effects of temperature on the dielectric properties at the competing mechanisms of polarisation and conductivity loss were clarified based on variations of the FDS curves. Considering the viscosity change of ageing transformer oil at low temperatures, the Arrhenius and VFT viscosity equations were used to achieve a fitting calculation in the different temperature zones. Based on the molecular/ion transition model in the force field and electric field, the characterisation relationships between the dynamic viscosity, DC conductivity, and test temperature of transformer oil were established. The limitations of conventional transformer oil equivalent dielectric relaxation models over a wide temperature range were finally clarified by combining the test findings of the DC conductivity over a wide temperature range with observed and simulated calculations. This paper provides an essential theoretical reference when using the FDS test to diagnose the insulation performance of oil‐immersed power equipment in extremely cold regions.

This study investigates the mechanical properties of cementitious composites with 3D-printed auxetic lattices, featuring negative Poisson’s ratios (auxetic behavior) in multiple directions. These lattices were fabricated using vat photopolymerization 3D printing, and three base materials with varying stiffness and deformation capacities were analyzed to determine their impact on the composites’ mechanical behavior. To unravel the reinforcing mechanisms of multidirectional auxetic lattices, which exhibit auxetic behavior in both planar and out-of-plane directions, X-ray computed tomography (X-ray CT) was utilized to analyze composite damage evolutions under different strain levels. The micro-CT characterization reveals that auxetic lattices more effectively constrain crack growth and dissipate energy by distributing stress evenly within the cement matrix. In contrast, due to lack of lateral confinement, the non-auxetic lattice reinforced composites primarily dissipate energy through extensive crack propagation and interfacial damage, leading to lower peak strength. When strain exceeding 5%, although the confinement from the auxetic behavior diminished with crack propagation, the lattice can still maintain the composite’s structural integrity, resulting in 1.7 times higher densification energy than conventional cement-based materials. These findings provide valuable insights for designing auxetic lattice-reinforced cementitious composites with enhanced load-bearing capacity and improved dissipation capabilities.

Background: Fruquintinib is a third-line and subsequent targeted therapy for patients with metastatic colorectal cancer (mCRC). Identifying survival predictors after fruquintinib is crucial for optimizing the clinical use of this medication. Objectives: We aimed to identify factors influencing the prognosis of patients with mCRC treated with fruquintinib and to leverage these insights to develop a nomogram model for estimating survival rates in this patient population. Design: Multicenter retrospective observational study. Methods: We collected patient data from January 2019 to October 2023, with one healthcare institution’s data serving as the training cohort and the other three hospitals’ data serving as the multicenter validation cohort. The nomogram for overall survival was calculated from Cox regression models, and variable selection was screened using the univariate Cox regression analysis with additional variables based on clinical experience. Model performance was measured by the concordance index (C-index), calibration curves, decision curve analyses (DCA), and utility (patient stratification into low-risk vs high-risk groups). Results: Data were ultimately collected on 240 patients, with 144 patients included in the training cohort and 96 included in the multicenter validation cohort. Predictors included in the nomogram were CA199, body mass index, T stage, the primary site of the tumor, and other metastatic and pathological differentiation. The C-index of the nomogram in the training set and multicenter validation was 0.714 and 0.729, respectively. The models were fully calibrated and their predictions aligned closely with the observed data. DCA curves indicated the promising clinical benefits of the predictive model. Finally, the reliability of the model was also verified through the risk classification using the nomogram. Conclusions: We constructed a nomogram for mCRC treated with fruquintinib based on six variables that may be used to assist in personalizing the use of the drug.

BackgroundCardiac rehabilitation (CR) is a safe, effective intervention for individuals with cardiovascular disease (CVD). However, a majority of eligible patients do not complete CR. Growing evidence suggests that home-based cardiac rehabilitation (HBCR) programs are comparable in effectiveness and safety with traditional center-based programs. More research is needed to explore different ways to deliver HBCR programs to patients with CVD. ObjectiveWe aimed to assess the feasibility and impact of a digital HBCR program (RecoveryPlus.Health) that integrates both telehealth and mHealth modalities on functional exercise capacity, resting heart rate, and quality of life among adults with CVD. MethodsThis 12-week prospective, single-arm remote clinical trial used a within-subject design. We recruited adults with CVD (aged ≥40 years) from the community with a CR-eligible diagnosis (stable angina pectoris, myocardial infarction, and heart failure) between May and August 2023. All enrolled patients referred to the RPH clinic in Roanoke, Texas, were included. The care team provided guideline-concordant CR services to study participants via two modalities: (1) a synchronous telehealth exercise training through videoconferencing; and (2) an asynchronous mobile health (mHealth) coaching app (RPH app). Baseline intake survey, electronic health record, and app log data were used to extract individual characteristics, care processes, and platform engagement data. Feasibility was measured by program completion rate and CR service use. Efficacy was measured by changes in the 6-minute walk test, resting heart rate, and quality of life (12-Item Short-Form Health Survey) before and after the 12-week program. Paired t tests were used to examine pre- and postintervention changes in the outcome variables. ResultsIn total, 162 met the inclusion criteria and 75 (46.3%) consented and were enrolled (mean age 64, SD 10.30 years; male: n=37, 49%; White: n=46, 61%). Heart failure was the most common diagnosis (37/75, 49%). In total, 62/75 (83%) participants completed the 12-week study and used the telehealth modality with 9.63 (SD 3.33) sessions completed, and 59/75 (79%) used the mHealth modality with 10.97 (SD 11.70) sessions completed. Post intervention, 50/62 (81%) participants’ performance in the 6-minute walk test had improved, with an average improvement of 40 (SD 63.39) m (95% CI 25.6-57.1). The average 12-Item Short-Form Health Survey’s physical and mental summary scores improved by 2.7 (SD 6.47) points (95% CI 1.1-4.3) and 2.2 (SD 9.09) points (95% CI 0.1-4.5), respectively. There were no changes in resting heart rate and no exercise-related adverse events were reported. ConclusionsThe RecoveryPlus.Health digital HBCR program showed feasibility and efficacy in a group of nationally recruited patients with CVD. The findings add to the evidence that a telehealth and mHealth dual-modality HBCR program may be a promising approach to overcome some of the main barriers to improving CR access in the United States. Trial RegistrationClinicalTrials.gov NCT05804500; https://clinicaltrials.gov/search?cond=NCT05804500

Throughout history, various odors have been harnessed to invigorate or relax the mind. The mechanisms underlying odors’ diverse arousal effects remain poorly understood. We conducted five experiments (184 participants) to investigate this issue, using pupillometry, electroencephalography, and the attentional blink paradigm, which exemplifies the limit in attentional capacity. Results demonstrated that exposure to citral, compared to vanillin, enlarged pupil size, reduced resting-state alpha oscillations and alpha network efficiency, augmented beta-gamma oscillations, and enhanced the coordination between parietal alpha and frontal beta-gamma activities. In parallel, it attenuated the attentional blink effect. These effects were observed despite citral and vanillin being comparable in perceived odor intensity, pleasantness, and nasal pungency, and were unlikely driven by semantic biases. Our findings reveal that odors differentially alter the small-worldness of brain network architecture, and thereby brain state and arousal. Furthermore, they establish arousal as a unique dimension in olfactory space, distinct from intensity and pleasantness.

Objective: To evaluate the effectiveness of low-level red light (LRL) in controlling the progression of myopia in children and adolescents. Methods: A randomized controlled trial was conducted from March 2022 to June 2022 at the Xuzhou First People's Hospital. A total of 73 children and adolescents with myopia, between the ages of 6 and 14, and meeting the inclusion criteria, were randomly divided into two groups. The experimental group wore single vision spectacles with LRL intervention, while the control group wore single vision spectacles alone. Spherical equivalent refraction (SER), axial length (AL), subfoveal choroidal thickness (SFCT), and best-corrected visual acuity (BCVA) were measured for the participants. Data analysis was performed using chi-square test, independent samples t-test, and Mann-Whitney U test. To compare the changes in SER and AL between groups, we utilized the Generalized Estimating Equations (GEE) model. Results: The experimental group was composed of 36 individuals, while the control group had 37. The mean age of the participants was 8.9 ± 2.0 years. No statistically significant distinctions in SER, AL and SFCT were observed between the two groups at baseline (P > 0.05). After 6 months of intervention, the experimental group's increase in SER (-0.01D; 95 % CI: -0.09, 0.06) was higher than that of the control group (-0.41D; 95 % CI: -0.51, -0.32), with a significance level of P < 0.001. Furthermore, the changes over time revealed significant differences between the two groups (Wald χ2group×time: 31.576, P < 0.001). The experimental group's AL increase (-0.02 mm; 95 % CI: -0.07, 0.03) was less than the control group's (0.22 mm; 95 % CI: 0.19, 0.25) (P < 0.001), with a significant difference over time between them (wald χ2group×time: 62.305, P < 0.001). SFCT change after 6 months in the experimental group was significantly greater (29.19 μm; 95 % CI: 18.48, 39.91) compared to that of the control group (-6.59 μm; 95 % CI: -14.28, 1.09) (P < 0.001). No adverse events were observed, and there was no evidence of fundus structural damage on OCT imaging. Conclusions: The findings suggest that low-level red light can effectively control myopia progression in children and adolescents within 6 months. No adverse reactions were observed.

Increasing the number of teats in sheep helps to improve the survival rate of sheep lambs after birth. In order to analyze the candidate genes related to the formation of multiple teats in Hu sheep, the present study was conducted to investigate the genetic pattern of multiple teats in Hu sheep. In this study, based on genome-wide data from 157 Hu sheep, Fst, xp-EHH, Pi and iHS signaling were performed, and the top 5% signal regions of each analyzed result were annotated based on the Oar_v4.0 for sheep. The results show that a total of 142 SNP loci were selected. We found that PTPRG, TMEM117 and LRP1B genes were closely associated with polypodium formation in Hu sheep, in addition, among the candidate genes related to polypodium we found genes such as TMEM117, SLC25A21 and NCKAP5 related to milk traits. The present study screened out candidate genes for the formation of multiple teats at the genomic level in Hu sheep.

Objective By assessing the genetic diversity and associated selective traits of Kirghiz sheep (KIR), we aim to uncover the mechanisms that contribute to sheep’s adaptability to the Pamir Plateau environment. Methods This study utilized Illumina Ovine SNP50 BeadChip data from KIR residing in the Pamir Plateau, Qira Black sheep (QBS) inhabiting the Taklamakan Desert, and commonly introduced breeds including Dorper sheep (DOR), Suffolk sheep (SUF), and Hu sheep (HU). The data was analyzed using principal component analysis, phylogenetic analysis, population admixture analysis, kinship matrix analysis, linkage disequilibrium analysis, and selective signature analysis. We employed four methods for selective signature analysis: fixation index (Fst), cross-population extended homozygosity (XP-EHH), integrated haplotype score (iHS), and nucleotide diversity (Pi). These methods aim to uncover the genetic mechanisms underlying the germplasm resources of Kirghiz sheep, enhance their production traits, and explore their adaptation to challenging environmental conditions. Results The test results unveiled potential selective signals associated with adaptive traits and growth characteristics in sheep under harsh environmental conditions, and annotated the corresponding genes accordingly. These genes encompass various functionalities such as adaptations associated with plateau, cold, and arid environment (ETAA1, UBE3D, TLE4, NXPH1, MAT2B, PPARGC1A, VEGFA, TBX15 and PLXNA4), wool traits (LMO3, TRPS1, EPHA5), body size traits (PLXNA2, EFNA5), reproductive traits (PPP3CA, PDHA2, NTRK2), and immunity (GATA3). Conclusion Our study identified candidate genes associated with the production traits and adaptation to the harsh environment of the Pamir Plateau in Kirghiz sheep. These findings provide valuable resources for local sheep breeding programs. The objective of this study is to offer valuable insights for the sustainable development of the Kirghiz sheep industry.

Abstract Diabetic kidney disease (DKD) is the leading cause of end‐stage kidney disease. DKD is a heterogeneous disease with complex pathophysiology where early endothelial dysfunction is associated with disease progression. The Tie2 receptor and Angiopoietin 1 and 2 ligands are critical for maintaining endothelial cell permeability and integrity. Tie2 signaling is negatively regulated by the endothelial specific transmembrane receptor Vascular Endothelial Protein Tyrosine Phosphatase (VEPTP). Genetic deletion of VEPTP protects from hypertension and diabetes induced renal injury in a mouse model of DKD. Here, we show that VEPTP inhibition with an extracellular domain targeting VEPTP antibody induced Tie2 phosphorylation and improved VEGF‐A induced vascular permeability both in vitro and in vivo. Treatment with the VEPTP blocking antibody decreased the renal expression of endothelial activation markers (Angpt2, Edn1, and Icam1) but failed to improve kidney function in db/db uninephrectomized ReninAAV DKD mice.

In this work, two bainitic steels with medium carbon content were developed by adding different Si. The mechanical properties of the two test steels and the stability of their retained austenite were studied, and the influence of Si in the steels was discussed. The results show that the film-like retained austenite of the high Si bainitic steel is greatly increased compared with that of the low Si bainitic steel and that the C content is increased, effectively preventing crack propagation and significantly improving the comprehensive mechanical properties. Due to the different Si content in the test steels, the orientation relationship of austenite in the steels has changed, and when the Si content is increased from 0.7 wt% to 1.4 wt%, the variant selection of bainite becomes weaker. Moreover, the increase of Si content not only inhibits the precipitation of carbides but also promotes the accumulation of C in the austenite, which improves the stability of the retained austenite.

Abstract This study aimed to explore the gut microbiota characteristics of ischemic and hemorrhagic stroke patients. A case–control study was conducted, and high-throughput sequencing of the V4–V5 region of 16S rRNA was used to analyze the differences in gut microbiota. The results showed that Proteobacteria was significantly increased in the ischemic stroke group compared with the healthy control group, while Fusobacteria was significantly increased in the hemorrhagic stroke group. In the ischemic stroke group, Butyricimonas, Alloprevotella, and Escherichia were significantly more abundant than in the healthy control group. In the hemorrhagic stroke group, Atopobium, Hungatella, Eisenbergiella, Butyricimonas, Odonbacter, Lachnociostridium, Alistipes, Parabacteroides, and Fusobacterium were significantly more abundant than in the healthy control group. Additionally, Alloprevotella, Ruminococcus, and Prevotella were significantly more abundant in the ischemic stroke group than in the hemorrhagic stroke group. The gut microbiota of ischemic and hemorrhagic stroke patients has significant diversity characteristics. These results provide new theoretical basis for exploring the prevention and treatment of different types of stroke through gut microbiota research.

Abstract The observed Southern Ocean sea surface temperature (SST) has experienced prominent inter-decadal variability nearly in phase with the Inter-decadal Pacific Oscillation (IPO), but less associated with the Atlantic Multidecadal Variability (AMV), challenging the prevailing view of Pacific-Atlantic synergistic effects. Yet, the mechanisms of distinct trans-hemispheric connections to the Southern Ocean remain indecisive. Here, by individually constraining the observed cold-polarity and warm-polarity IPO and AMV SSTs in a climate model, we show that the IPO is influential in initiating a basin-wide Southern Ocean response, with the AMV secondary. A tropical Pacific-wide cooling triggers a basin-scale Southern Ocean cold episode through a strong Rossby wave response to the north-to-south cross-equatorial weakened Hadley circulation. By contrast, due to the competing role of tropical Pacific cooling, an Atlantic warming partly cools the Southern Ocean via a weak Rossby wave response to the south-to-north cross-equatorial enhanced Hadley circulation. Conversely, tropical Pacific warming leads to a warm Southern Ocean episode. Our findings highlight that properly accounting for the tropical Pacific SST variability may provide a potential for skillful prediction of Southern Ocean climate change and more reliable estimates of climate sensitivity, currently overestimated by the misrepresented Southern Ocean warming.

Abstract Background Enhancing angiogenesis may be an effective strategy to promote functional recovery after ischemic stroke. Inflammation regulates angiogenesis. Microglia are crucial cells that initiate inflammatory responses after various brain injuries. Long noncoding RNA nuclear paraspeckle assembly transcript 1 (NEAT1) plays a role in regulating brain injury. This study aimed to explore the effects of NEAT1-regulated microglial polarization on the neovascularization capacity of cerebrovascular endothelial cells and the underlying molecular regulatory mechanisms. Methods Mouse cerebral arterial endothelial cells (mCAECs) were co-cultured with BV-2 cells in different groups using a Transwell system. NEAT1 expression levels were measured by fluorescence quantitative reverse transcription PCR. Levels of IL-1β, IL-6, TNF-α, Arg-1, IL-4, and IL-10 were determined using ELISA. Expression levels of CD86 and CD163 were detected by immunofluorescence. The neovascularization capacity of mCAECs was assessed using CCK-8, Transwell, Transwell-matrigel, and tube formation assays. Label-free quantification proteomics was carried out to identify differentially expressed proteins. Protein levels were measured by Western blotting. Results NEAT1 overexpression induced M1 polarization in BV-2 cells, whereas NEAT1 knockdown blocked lipopolysaccharide-induced M1 polarization in microglia. NEAT1-overexpressing BV-2 cells suppressed the angiogenic ability of mCAECs, and NEAT1-knocking BV-2 cells promoted the angiogenic ability of mCAECs under lipopolysaccharide treatment. Label-free quantitative proteomic analysis identified 144 upregulated and 131 downregulated proteins that were induced by NEAT1 overexpression. The AMP-activated protein kinase (AMPK) signaling pathway was enriched in the Kyoto Encyclopedia of Genes and Genomes analysis of the differentially expressed proteins. Further verification showed that NEAT1 inactivated the AMPK signaling pathway. Moreover, the AMPK activator 5-aminoimidazole-4-carboxamide ribonucleotide reversed the effect of NEAT1 on BV-2 polarization and the regulatory effect of NEAT1-overexpressing BV-2 cells on the angiogenic ability of mCAECs. Conclusions NEAT1 inhibits the angiogenic activity of mCAECs by inducing M1 polarization of BV-2 cells through the AMPK signaling pathway. This study further clarified the impact and mechanism of NEAT1 on microglia and the angiogenic ability of cerebrovascular endothelial cells.

Abstract Urban water bodies can effectively mitigate the urban heat island effect and thus enhance the climate resilience of urban areas. The cooling effect of different water bodies varies, however, the cooling heterogeneity of different sections of a single watercourse or river network is rarely considered. Based on various satellite images, geospatial approaches and statistical analyses, our study confirmed the cooling heterogeneity from spatial and seasonal perspectives of the Suzhou Outer-city River in detail in the urban area of Suzhou, China. The cooling effect of the river was observed in the daytime in four seasons, and it is strongest in summer, followed by spring and autumn, and weakest in winter. The combination of the width of the river reach, the width and the NDVI value of the adjacent green space can explain a significant part of the cooling heterogeneity of the different river sections in different seasons. Land surface temperature (LST) variations along the river are more related to the width of the river reach, but the variations of the cooling distance are more related to the adjacent green space. The cooling effect of a river reach could be enhanced if it is accompanied by green spaces. In addition, the cooling effect of a looping river is stronger on the inside area than on the outside. The methodology and results of this study could help orient scientific landscape strategies in urban planning for cooler cities.

Abstract Background Missed nursing care is a pervasive issue in hospitals, nursing homes, and communities, posing a significant threat to patient safety and the quality of nursing care. It has adverse effects on patient satisfaction and the motivation of nursing staff. Understanding the causes and nature of these care omissions in clinical settings is essential for implementing effective interventions. This study aims to develop and validate a tool for assessing missed nursing care in adult intensive care units. Methods Semi-structured interviews, expert consultations conducted via the Delphi method and item analysis were used to develop the initial scale. Our analysis involved data collected from 400 nurses and employed correlation coefficient analysis, critical ratio assessment, Cronbach’s α coefficient evaluation, discrete trend analysis, and factor analysis, which were grounded in both classical test theory and item response theory, allowing us to scrutinize and refine the items in the scale. To validate the scale, we conveniently sampled 550 nurses and assessed structural validity, internal reliability, split-half reliability, and test-retest reliability to ensure the scale’s robustness and accuracy. Results The Missed Intensive Nursing Care Scale (MINCS) comprises three distinct components. Part A serves to collect general information about the participants. In Part B, the missed care elements are categorized into five domains, following the framework of Maslow’s hierarchy of needs theory: physiology, safety, belongingness, esteem, and cognition. Part C is dedicated to detailing the reasons behind missed care, which encompass labor resources, material resources, communication factors, and managerial factors. Remarkably, the Cronbach’s α coefficient for the MINCS stands at an impressive 0.951, with S-CVI values of 0.988 and 0.977 in Part B and C, respectively, underscoring the scale’s exceptional reliability and validity. This demonstrates the scale’s effectiveness in measuring missed nursing care while upholding rigorous standards of quality. Conclusions The MINCS emerges as a robust and dependable instrument for quantifying instances of missed care within the ICU. Its efficacy makes it a valuable resource for informing the development of strategies aimed at averting and mitigating the adverse effects associated with missed nursing care.

Abstract Pulmonary fibrosis (PF) is a progressive interstitial inflammatory disease with a high mortality rate. Patients with PF commonly experience a chronic dry cough and progressive dyspnoea for years without effective mitigation. The pathogenesis of PF is believed to be associated with dysfunctional macrophage polarization, fibroblast proliferation, and the loss of epithelial cells. Thus, it is of great importance and necessity to explore the interactions among macrophages, fibroblasts, and alveolar epithelial cells in lung fibrosis, as well as in the pro-fibrotic microenvironment. In this review, we discuss the latest studies that have investigated macrophage polarization and activation of non-immune cells in the context of PF pathogenesis and progression. Next, we discuss how profibrotic cellular crosstalk is promoted in the PF microenvironment by multiple cytokines, chemokines, and signalling pathways. And finally, we discuss the potential mechanisms of fibrogenesis development and efficient therapeutic strategies for the disease. Herein, we provide a comprehensive summary of the vital role of macrophage polarization in PF and its profibrotic crosstalk with fibroblasts and alveolar epithelial cells and suggest potential treatment strategies to target their cellular communication in the microenvironment.

Since the national carbon market in China started trading in 2021, only over 2000 enterprises in the power generation industry have participated in the trading, with a small cumulative trading volume. There is an urgent demand for market expansion. Currently, the Chinese economy is still in the recovery stage, facing significant employment pressure. In order to avoid a large negative impact of the expansion of the Chinese carbon market on the economy, key industries should be systematically included in the national carbon market. We developed a social accounting matrix (SAM) multiplier analysis based on industry grouping and consider two scenarios: first, each key industry reduces CO2 emissions by 1 ton, and second, each key industry reduces CO2 emissions by 1 %. For the first scenario, we calculate the marginal value added and employment impacts of carbon reduction. For the second scenario, the impact of carbon reduction on the elasticity of value added and the elasticity of employment are calculated. Industries with the higher added value and employment losses per unit of carbon reduction should be included later in China's national carbon market. The sorting results of the two scenarios can mutually corroborate each other. Our order of inclusion is different from the market's expectations, and the results are also different from previous relevant studies. On the one hand, we not only calculates the direct economic impact of key industries included in the national carbon market but also calculates the indirect and induced economic impacts. On the other hand, we used a “from the outside to the inside” planning method rather than “from the inside to the outside.” We recommend sequentially including the remaining seven key industries in the national carbon market according to the order in this article.

Objectives This research first investigated the effect of mesoporous silica nanoparticles (nMS) carrying chlorhexidine and silver (nMS-nAg-Chx) on periodontitis-related biofilms. This study aimed to investigate (1) the antibacterial activity on Porphyromonas gingivalis (P. gingivalis) biofilm; (2) the suppressing effect on virulence of P. gingivalis biofilm; (3) the regulating effect on periodontitis-related multispecies biofilm.Methods Silver nanoparticles (nAg) and chlorhexidine (Chx) were co-loaded into nMS to form nMS-nAg-Chx. Inhibitory zone test and minimum inhibitory concentration (MIC) against P. gingivalis were tested. Growth curves, crystal violet (CV) staining, live/dead staining and scanning electron microscopy (SEM) observation were performed. Biofilm virulence was assessed. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay and Quantitative Real Time-PCR (qPCR) were performed to validate the activity and composition changes of multispecies biofilm (P. gingivalis, Streptococcus gordonii and Streptococcus sanguinis).Results nMS-nAg-Chx inhibited P. gingivalis biofilm dose-dependently (p

AbstractReservoir impoundment is the main factor inducing reservoir landslides, it is essential to obtain the dynamic landslide susceptibility by considering hydraulic factors. In this paper, we proposed the use of the original and revised logistic regression models (machine learning methods) to analyze the landslide susceptibility after the second stage of reservoir impoundment. Data of active unstable slopes before the first stage of reservoir impoundment were used to train the models. The results indicated that the two models both performed well with high accuracy. The revised logistic regression model performed better than the original logistic regression model in two aspects. Firstly, TPR and AUC of the revised model is 0.771 and 0.906 which is obviously higher than the original model of 0.743 and 0.896. Secondly, the revised model can predict the unstable slopes after reservoir impoundment which the original model can’t predict. The former could be used to obtain the dynamic landslide susceptibility in reservoir areas after different stages of reservoir impoundment and predict the potential reactivated unstable slopes more precisely due to hydraulic factors.

The objective of this study is to analyze environmental genetic selection signals in large-scale sheep populations with conflicting environmental adaptations, aiming to identify and isolate genes associated with environmental adaptations in sheep populations. Kirghiz sheep, which inhabit high-altitude environments year-round, demonstrate the ability to adapt to extreme conditions. In this study, 42 Kirghiz sheep, 24 Tien-Shan in Kyrgyzstan sheep, 189 Qira black sheep, and 160 Chinese Merino sheep were genotyped using Illumina Ovine SNP50K chip. Regions exhibiting a selection signal threshold of 5%, as well as PI analysis and haplotype statistical scanning gene data were annotated, and intersecting genes were identified as candidate genes. Through Fst and haplotype statistical analysis revealed the key gene PDGFD and its vicinity’s impact on fat deposition in sheep tails. Additionally, Fst and PI analysis uncovered genes related to high-altitude adaptation as well as those linked to animal growth and reproduction.Further GO and KEGG enrichment pathway analyses unveiled pathways associated with high-altitude adaptation such as negative regulation of peptidyl-tyrosine phosphorylation and xenobiotic metabolism processes.This investigation into the adaptability of Kirghiz sheep provides theoretical support and practical guidance for the conservation and genetic enhancement of Kirghiz sheep germplasm resources.

BackgroundThe design of femoral stem prostheses requires a precise understanding of the femoral marrow cavity. Traditional measurements of morphological parameters in the upper femur, particularly the medullary cavity and cortical region, are primarily based on coronal and sagittal axes, which may not fully capture the true three-dimensional structure of the femur.MethodsPropose a Monte Carlo-based method for a more comprehensive analysis of the femoral marrow cavity, using CT scans of femurs from a selected group of patients. The study aimed to define and calculate anatomically semantic morphological parameters to enhance the understanding of the femoral marrow cavity's anatomical morphological changes, ultimately improving the design and clinical selection of femoral stem prostheses. To enhance the accuracy of femoral stem prosthesis design, this study aims to develop a Monte Carlo-based method for a more comprehensive analysis of the femoral marrow cavity. The proposed method transforms the non-random problem of determining cross-sectional size into a random issue, allowing for the calculation of the size of the medullary cavity and cortical region. Anatomically semantic morphological parameters are then defined, calculated, and analyzed.ResultsThe experimental results indicate that the newly defined parameters complement existing ones, providing a more rational scientific basis for understanding the anatomical morphological changes of the femoral marrow cavity.ConclusionThis research offers essential scientific theoretical support for improved morphologic research, design, and clinical selection of femoral stem prostheses. It holds significant importance and application value in clinical practice, contributing to a more accurate and comprehensive understanding of femoral anatomy for prosthetic design.