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PurposeTo explore molecular mechanisms affecting nutritional risk and neurodevelopment in children with congenital heart disease (CHD) by combining transcriptome and metabolome analysis.MethodsA total of 26 blood and serum samples from 3 groups of children with CHD low nutritional risk combined with normal neurodevelopment (group A), low nutritional risk combined with neurodevelopmental disorders (group B) and high nutritional risk combined with normal neurodevelopment (group C) were analyzed by transcriptome and metabolomics to search for differentially expressed genes (DEGs) and metabolites (DEMs). Functional analysis was conducted for DEGs and DEMs. Further, the joint pathway analysis and correlation analysis of DEGs and DEMs were performed.ResultsA total of 362 and 1,351 DEGs were detected in group B and C compared to A, respectively. A total of 6 and 7 DEMs were detected in group B and C compared to A in positive mode, respectively. There were 39 and 31 DEMs in group B and C compared to A in negative mode. Transcriptomic analysis indicated that neurodevelopment may be regulated by some genes such as NSUN7, SLC6A8, CXCL1 and LCN8, nutritional risk may be regulated by SLC1A3 and LCN8. Metabolome analysis and joint pathway analysis showed that tryptophan metabolism, linoleic and metabolism and glycerophospholipid metabolism may be related to neurodevelopment, and glycerophospholipid metabolism pathway may be related to nutritional risk.ConclusionBy integrating transcriptome and metabolome analyses, this study revealed key genes and metabolites associated with nutritional risk and neurodevelopment in children with CHD, as well as significantly altered pathways. It has important clinical translational significance.

IntroductionBacteriophages have been shown to penetrate biofilms and replicate if they find suitable host cells. Therefore, these viruses appear to be a good option to tackle the biofilm problem and complement or even substitute more conventional antimicrobials. However, in order to successfully remove biofilms, in particular mature biofilms, phages may need to be administered along with other compounds. Phage-derived proteins, such as endolysins or depolymerases, offer a safer alternative to other compounds in the era of antibiotic resistance.MethodsThis study examined the interactions between phage Kayvirus rodi with a polysaccharide depolymerase (Dpo7) from another phage (Rockefellervirus IPLA7) against biofilms formed by different Staphylococcus aureus strains, as determined by crystal violet staining, viable cell counts and microscopy analysis.Results and discussionOur results demonstrated that there was synergy between the two antimicrobials, with a more significant decreased in biomass and viable cell number with the combination treatment compared to the phage and enzyme alone. This observation was confirmed by microscopy analysis, which also showed that polysaccharide depolymerase treatment reduced, but did not eliminate extracellular matrix polysaccharides. Activity assays on mutant strains did not identify teichoic acids or PNAG/PIA as the exclusive target of Dpo7, suggesting that may be both are degraded by this enzyme. Phage adsorption to S. aureus cells was not significantly altered by incubation with Dpo7, indicating that the mechanism of the observed synergistic interaction is likely through loosening of the biofilm structure. This would allow easier access of the phage particles to their host cells and facilitate infection progression within the bacterial population.

IntroductionAcute myeloid leukemia (AML) is an aggressive blood cancer with high heterogeneity and poor prognosis. Although the metabolic reprogramming of nicotinamide adenine dinucleotide (NAD) has been reported to play a pivotal role in the pathogenesis of acute myeloid leukemia (AML), the prognostic value of NAD metabolism and its correlation with the immune microenvironment in AML remains unclear.MethodsWe utilized our large-scale RNA-seq data on 655 patients with AML and the NAD metabolism-related genes to establish a prognostic NAD metabolism score based on the sparse regression analysis. The signature was validated across three independent datasets including a total of 1,215 AML patients. ssGSEA and ESTIMATE algorithms were employed to dissect the tumor immune microenvironment. Ex vivo drug screening and in vitro experimental validation were performed to identify potential therapeutic approaches for the high-risk patients. In vitro knockdown and functional experiments were employed to investigate the role of SLC25A51, a mitochondrial NAD+ transporter gene implicated in the signature.ResultsAn 8-gene NAD metabolism signature (NADM8) was generated and demonstrated a robust prognostic value in more than 1,800 patients with AML. High NADM8 score could efficiently discriminate AML patients with adverse clinical characteristics and genetic lesions and serve as an independent factor predicting a poor prognosis. Immune microenvironment analysis revealed significant enrichment of distinct tumor-infiltrating immune cells and activation of immune checkpoints in patients with high NADM8 scores, acting as a potential biomarker for immune response evaluation in AML. Furthermore, ex vivo drug screening and in vitro experimental validation in a panel of 9 AML cell lines demonstrated that the patients with high NADM8 scores were more sensitive to the PI3K inhibitor, GDC-0914. Finally, functional experiments also substantiated the critical pathogenic role of the SLC25A51 in AML, which could be a promising therapeutic target.ConclusionOur study demonstrated that NAD metabolism-related signature can facilitate risk stratification and prognosis prediction in AML and guide therapeutic decisions including both immunotherapy and targeted therapies.

Based on the configuration theory, this paper discusses the multiple concurrent causes and causal complex mechanisms affecting the performance differences among different new farmers. Using the fuzzy set qualitative comparative analysis method, taking 40 cases of CCTV’s “ZHI FU JING” column as samples, the paper analyzes the necessary conditions for new farmers to produce high performance by the anthefactory-variable configuration composed of human capital, social capital, psychological capital, entrepreneurial learning and entrepreneurial opportunity identification. The results show that: (1) high human capital is the necessary core condition for new farmers to produce high entrepreneurial performance, lack of high entrepreneurial learning and lack of high entrepreneurial opportunity identification is the core necessary condition for low entrepreneurial performance; (2) the driving mechanism of new farmers’ high entrepreneurial performance is divided into three paths, and the driving mechanism of new farmers’ low entrepreneurial performance is divided into two paths; and (3) the ways of inhibiting new farmers’ performance and promoting their performance are asymmetrical.

Warfarin is an anticoagulant that requires INR-based dosage adjustment. Ascorbic acid may impair warfarin effectiveness according to limited literature. We report a rare case of a 63-year-old woman with an aortic valve replacement history who developed warfarin resistance after taking ascorbic acid for anemia following breast cancer surgery. Despite increasing the warfarin dose from 6 mg to 10 mg daily, her INR remained below the therapeutic range. After ruling out other causes of warfarin resistance, we discontinued ascorbic acid and observed a rapid increase in INR to target values. The temporal relationship and the absence of other confounding factors confirmed the causality of ascorbic acid in this case. We recommend that patients concomitantly taking vitamin C and warfarin should monitor their INR values closely and discontinue ascorbic acid as soon as possible if they exhibit signs of warfarin resistance.

ObjectiveThis study recalculates the carbon emissions of urban and rural residents in China, analyzing the dynamic evolution trends of urban and rural carbon emissions. It explores the spatial spillover effects centered around the inequality in carbon emissions between urban and rural areas.MethodsThe study calculates the carbon emissions of urban and rural residents in each province based on the IPCC method. Non-parametric kernel density estimation is employed to depict the dynamic evolution characteristics of national, urban, and rural carbon emissions. The Theil Index is used to measure the disparities in urban and rural carbon emissions in major strategic regions, further applying the Theil Index to evaluate the inequality of urban and rural carbon emissions across provinces. This helps identify the driving factors affecting the inequality of urban and rural carbon emissions and their spatio-temporal effects.FindingCarbon emissions from urban and rural residents in China present a divergent development pattern. Urban emissions have increased, with inter-provincial disparities widening; rural emissions tend to stabilize, with slight growth in inter-provincial gaps. The overall inequality of carbon emissions in various regions of China experiences a three-phase journey of rise, decline, and stabilization. Urban inequality first increases then decreases, while rural inequality gradually lessens, showing clear regional and urban-rural differences. Market and government factors significantly impact the inequality of urban and rural carbon emissions. The development of the digital economy aids in reducing inequality and generates significant spatial spillover effects. The relationship between economic development level and carbon emission inequality is U-shaped. Industrial structure optimization can reduce urban-rural inequality, but its spatial spillover effect is not significant. Government intervention has limited effects, while environmental regulations may increase inequality. Opening up to the outside world helps reduce inequality, and the impact of population density is complex.

BackgroundMyopia poses a global health concern and is influenced by both genetic and environmental factors. The incidence of myopia tends to increase during infectious outbreaks, such as the COVID-19 pandemic. This study examined the screen-time behaviors among Chinese children and adolescents and investigated the efficacy of artificial intelligence (AI)-based alerts in modifying screen-time practices.MethodsA cross-sectional analysis was performed using data from 6,716 children and adolescents with AI-enhanced tablets that monitored and recorded their behavior and environmental light during screen time.ResultsThe median daily screen time of all participants was 58.82 min. Among all age groups, elementary-school students had the longest median daily screen time, which was 87.25 min and exceeded 4 h per week. Children younger than 2 years engaged with tablets for a median of 41.84 min per day. Learning accounted for 54.88% of participants’ screen time, and 51.03% (3,390/6,643) of the participants used tablets for 1 h at an average distance

Introduction: Achieving peak carbon dioxide emissions and carbon neutrality is an extensive and profound systematic economic and social change. Through market-oriented financial means, green finance has moved forward the effective governance port, curbed polluting investment and promoted technological progress such as green low-carbon, energy conservation and environmental protection, which has become a powerful starting point to support the practice of low-carbon development.Methods: Based on the panel data of 30 provinces in China (except Tibet, Hongkong, Macau and Taiwan Province) from 2004 to 2021, this paper calculates the development level of green finance in China provinces by using entropy weight method, and on this basis, uses mathematical statistical model to verify the impact of green finance and its sub-dimensions on carbon emissions and the regulatory effect of heterogeneous environmental regulation tools.Results: The results show that the development of green finance has a significant inhibitory effect on carbon emissions during the investigation period, and there is a time lag effect. After a series of robustness tests and considering endogenous problems, this conclusion still holds. From the results of heterogeneity analysis, the carbon emission reduction effect of green credit is the most obvious, and the impact of green finance on carbon emission is slightly different in different regions. Besides, Command-controlled environmental regulation tools and public participation environmental regulation tools play a positive regulatory role in the transmission path of green finance’s impact on carbon emissions, but market-driven environmental regulation tools cannot effectively enhance the carbon emission reduction effect of green finance development.Discussion: The research results of this paper provide a basis for the government to formulate flexible, accurate, reasonable and appropriate green financial policies, help to strengthen the exchange and cooperation between regions in reducing carbon and fixing carbon, and actively and steadily promote China’s goal of “peak carbon dioxide emissions, carbon neutrality”.

Smoking is a leading risk factor of chronic obstructive pulmonary disease (COPD), that is characterized by chronic lung inflammation, tissue remodeling and emphysema. Although inflammation is critical to COPD pathogenesis, the cellular and molecular basis underlying smoking-induced lung inflammation and pathology remains unclear. Using murine smoke models and single-cell RNA-sequencing, we show that smoking establishes a self-amplifying inflammatory loop characterized by an influx of molecularly heterogeneous neutrophil subsets and excessive recruitment of monocyte-derived alveolar macrophages (MoAM). In contrast to tissue-resident AM, MoAM are absent in homeostasis and characterized by a pro-inflammatory gene signature. Moreover, MoAM represent 46% of AM in emphysematous mice and express markers causally linked to emphysema. We also demonstrate the presence of pro-inflammatory and tissue remodeling associated MoAM orthologs in humans that are significantly increased in emphysematous COPD patients. Inhibition of the IRAK4 kinase depletes a rare inflammatory neutrophil subset, diminishes MoAM recruitment, and alleviates inflammation in the lung of cigarette smoke-exposed mice. This study extends our understanding of the molecular signaling circuits and cellular dynamics in smoking-induced lung inflammation and pathology, highlights the functional consequence of monocyte and neutrophil recruitment, identifies MoAM as key drivers of the inflammatory process, and supports their contribution to pathological tissue remodeling.

Purpose: This study aimed to investigate the features of progressive keratoconus by means of machine learning.Methods: In total, 163 eyes from 127 patients with at least 3 examination records were enrolled in this study. Pentacam HR was used to measure corneal topography. Steepest meridian keratometry (K1), flattest meridian keratometry (K2), steepest anterior keratometry (Kmax), central corneal thickness (CCT), thinnest corneal thickness (TCT), anterior radius of cornea (ARC), posterior elevation (PE), index of surface variation (ISV), and index of height deviation (IHD) were input for analysis. Support vector machine (SVM) and logistic regression analysis were applied to construct prediction models.Results: Age, PE, and IHD showed statistically significant differences as the follow-up period extended. K2, PE, and ARC were selected for model construction. Logistic regression analysis presented a mean area under the curve (AUC) score of 0.780, while SVM presented a mean AUC of 0.659. The prediction sensitivity of SVM was 52.9%, and specificity was 79.0%.Conclusion: It is feasible to use machine learning to predict the progression and prognosis of keratoconus. Posterior elevation exhibits a sensitive prediction effect.

Gastric precancerous lesions (GPL) are a major health concern worldwide due to their potential to progress to gastric cancer (GC). Understanding the mechanism underlying the transformation from GPL to GC can provide a fresh insight for the early detection of GC. Although chronic inflammation is prevalent in the GPL, how the inflammatory microenvironment monitored the progression of GPL-to-GC are still elusive. Inflammation has been recognized as a key player in the progression of GPL. This review aims to provide an overview of the inflammatory microenvironment in GPL and its implications for disease progression and potential therapeutic applications. We discuss the involvement of inflammation in the progression of GPL, highlighting Helicobacter pylori (H. pylori) as a mediator for inflammatory microenvironment and a key driver to GC progression. We explore the role of immune cells in mediating the progression of GPL, and focus on the regulation of inflammatory molecules in this disease. Furthermore, we discuss the potential of targeting inflammatory pathways for GPL. There are currently no specific drugs for GPL treatment, but traditional Chinese Medicine (TCM) and natural antioxidants, known as antioxidant and anti-inflammatory properties, exhibit promising effects in suppressing or reversing the progression of GPL. Finally, the challenges and future perspectives in the field are proposed. Overall, this review highlights the central role of the inflammatory microenvironment in the progression of GPL, paving the way for innovative therapeutic approaches in the future.

Introduction: Strengthening the early warning of greenhouse gas emissions from agriculture is an important way to achieve Goal 13 of the Sustainable Development Goals. Agricultural carbon emissions are an important part of greenhouse gases, and accelerating the development of green and low-carbon agriculture is of great significance for China to achieve high-quality economic development and the goal of “carbon neutrality in peak carbon dioxide emissions”.Methods: By measuring the total agricultural carbon emissions in China and seven administrative regions from 2000 to 2021, the paper analyzes the influencing factors of agricultural carbon emissions in China by using STIRPAT environmental pressure model, and on this basis, predicts the peak trend of agricultural carbon emissions in China under different development scenarios by using the extreme learning machine model optimized by genetic algorithm.Results: The results showed that the extreme learning machine model improved by the genetic algorithm can overcome the shortcoming that the extreme learning machine model is easy to fall into the local optimal solution, thus obtaining higher prediction accuracy. At the same time, from 2000 to 2021, the total agricultural carbon emissions in China showed a continuous fluctuation trend, and due to the constraints of the agricultural economic level, agricultural industrial structure, and agricultural human capital, the agricultural carbon emissions showed spatial differentiation. It is worth noting that, in the context of green development, the agricultural carbon emissions of the seven regions in China all have the potential to achieve the “peak carbon dioxide emissions” goal in 2030, with only a slight difference at the peak.Discussion: The research results of this paper provide evidence for the government to formulate flexible, accurate, reasonable and appropriate agricultural carbon reduction policies, which is helpful to strengthen the exchanges and cooperation of regional agricultural and rural carbon reduction and fixation, and actively and steadily promote China's agriculture to achieve the goal of “peak carbon dioxide emissions carbon neutrality”.

Introduction: Improving energy efficiency is significant for achieving carbon emission reduction and promoting the transformation of green economic development. In the sustainable development framework set out in the 2030 Agenda for Sustainable Development, Goal 7.3 explicitly aims to double the global rate of energy efficiency improvement by 2030. The rapid development of digital technology, along with its universality and penetrative characteristics, has provide a feasible solution for improving energy efficiency and environmental conditions. However, the theoretical understanding of the impact and underlying logic of digital technology on energy efficiency remains unclear.Methods: Based on the panel data of 30 provinces in China from 2006 to 2021, this paper adopts econometric methods, including two-way fixed effect, instrumental variable method, and Driscoll-Kraay standard error. It investigates the influence of digital technology on energy efficiency and its internal mechanism from single factor and all factor levels.Result: The results show that Digital technology, represented by industrial robots, significantly improves energy efficiency, whether measured by the energy consumption intensity of GDP or the total-factor energy efficiency estimated using the SBM-GML model. The results still hold even after conducting endogeneity tests and robustness tests. Digital technology can improve energy efficiency by increasing virtual industrial agglomeration and promoting outward foreign direct investment.Discussion: In addition to promoting the theoretical understanding of the impact of digital technology on energy efficiency and exploring its mechanism, this paper also provides empirical evidence for policy makers and enterprises to formulate effective measures and strategies to improve energy efficiency under the background of digital economy.

IntroductionGlobal warming presents significant challenges to the sustainable development of human society. Accelerating the achievement of carbon peak and neutrality is the vision for creating a global ecological community with a shared future. The development of digital technology provides us with the direction of action.MethodsBased on panel data from 276 cities in China from 2011 to 2020, principal component analysis was used to measure the basic state of digital technology at the city level, and the twoway fixed effects model and instrumental variable method to verify the impact of digital technology on carbon emissions from the perspective of technology diffusion.ResultsThe results show that the deep diffusion of digital technology in the real economy sector is helpful to improve productivity and carbon efficiency, thus significantly reducing carbon emissions. The role of digital technologies in reducing carbon emissions is heterogeneous. The results of the sub-sample test show that digital technology has a stronger emission reduction effect in large-scale cities, resource-based cities, smart cities and emission trading policy pilot areas. Digital technology can reduce carbon emissions by improving energy efficiency, promoting green technology innovation, and promoting virtual agglomeration.DiscussionsThe contribution of this paper is that it not only reveals that digital technology can reduce carbon emissions but also analyzes the emission reduction path of digital technology from a new perspective. The conclusion of this paper has implications for accelerating the diffusion of digital technology in the real economy sector to accelerate the realization of green production and cope with climate change.

Background and AimsAnesthetics such as propofol, esketamine and nalbuphine are used during the upper gastrointestinal endoscopy to achieve and maintain the desired sedation level. The aim of the study was to evaluate the effectiveness and safety of propofol-nalbuphine and propofol-esketamine in children.MethodsA multi-centered study was performed at three tertiary class-A hospitals. Children between 3 and 12 years old undergoing diagnostic painless upper gastrointestinal endoscopy were included and randomly divided into esketamine or nalbuphine group to estimate the primary outcome of successful endoscope insertion. The patients were given esketamine 0.5 mg/kg and propofol 2 mg/kg intravenously in esketamine group, with nalbuphine 0.2 mg/kg and propofol 2 mg/kg in the nalbuphine group. The primary outcome was success rate for the first attempt of endoscope insertion in each group. Secondary outcomes included the safety of both anesthesia regimens and gastroenterologist's satisfaction. We used the Face, Leg, Activity, Cry and Consolability (FLACC) scale to evaluate the level of pain before and during the procedure and the Pediatric Anesthesia Emergence Delirium (PAED) scale to assess the level of agitation and delirium after awakening from anesthesia.ResultsAmong 246 patients, 200 were randomly included in the final intention-to-treat analysis, with 100 patients in each group. The success rate for the first attempt of endoscope insertion in the esketamine group was higher than the nalbuphine group (97% vs. 66%; P

IntroductionTo investigate the clinical characteristics and disease outcomes of a pedigree with compound heterozygous mutations in the SLC22A5 gene.MethodsSerum acylcarnitine profiles of patients were analyzed using tandem mass spectrometry. DNA samples isolated from patients and their first-degree relatives were subjected to high-throughput sequencing, and mutations were validated using Sanger sequencing.ResultsThe proband, a 4-month-old girl, presented with seizure episodes and mild cardiac hypertrophy and was diagnosed with primary carnitine deficiency (PCD), with carnitine levels of 5.165 mol/L. Her brother, a 6-year-and 4-month-old boy, was also diagnosed with PCD with serum-free carnitine levels of 1.014 mol/L (reference values 10–60 mol/L). Compound heterozygous mutations (c.760C > T [p.R254X] and c.825G > A [p.W275X]) were detected in the SLC22A5 gene in both patients and were inherited from the mother and father, respectively. Oral L-carnitine significantly improved or resolved the clinical symptoms.ConclusionChildren with compound mutations in SLC22A5 may present different clinical manifestations, particularly at different ages. Early clinical manifestations have a greater impact on the organs and may cause irreversible damage. PCD can cause epilepsy and dilated cardiomyopathy. Tandem mass spectrometry and high-throughput sequencing are recommended to confirm the diagnosis. Early L-carnitine supplementation can improve symptoms and reverse organ damage in some children. Tandem mass spectrometry should be used to screen for newborns with a family history of PCD.

Purpose: To compare bilateral differences in corneal biomechanics between keratoconus and normal eyes.Methods: In this case-control study, 346 eyes of 173 patients (aged 22.1 ± 6.1 years) with keratoconus (KC group) and 378 eyes of 189 patients (aged 26.7 ± 5.6 years) with ametropia (control group) were enrolled. Corneal tomography and biomechanical properties were examined using Pentacam HR and Corvis ST, respectively. The corneal biomechanical parameters were compared between eyes with forme fruste keratoconus (FFKC) and normal eyes. Bilateral differences in corneal biomechanical parameters were compared between the KC and control groups. Receiver operating characteristic (ROC) analysis was used to assess discriminative efficacies.Results: The areas under the ROC curves (AUROCs) of stiffness parameter at the first applanation (SP-A1) and Tomographic and Biomechanical Index (TBI) for identifying FFKC were 0.641 and 0.694, respectively. The bilateral differential values of major corneal biomechanical parameters were significantly increased in the KC group (all p < 0.05), except for the Corvis Biomechanical Index (CBI). The AUROCs of the bilateral differential values of the deformation amplitude ratio at 2 mm (ΔDAR2), Integrated Radius (ΔIR), SP-A1 (ΔSP-A1), and the maximum inverse concave radius (ΔMax ICR) for discriminating keratoconus were 0.889, 0.884, 0.826, and 0.805, respectively. The Logistic Regression Model-1 (comprising of ΔDAR2, ΔIR, and age) and the Logistic Regression Model-2 (comprising of ΔIR, ΔARTh, ΔBAD-D, and age) had AUROCs of 0.922 and 0.998, respectively, for discriminating keratoconus.Conclusion: The bilateral asymmetry of corneal biomechanics was significantly increased in keratoconus compared with normal eyes, which may be helpful for the early detection of keratoconus.

BackgroundSnail family transcriptional repressor 2 (SNAI2) is a transcription factor that induces epithelial to mesenchymal transition in neoplastic epithelial cells. It is closely related to the progression of various malignancies. However, the significance of SNAI2 in human pan-cancer is still largely unknown.MethodsThe Cancer Genome Atlas (TCGA), Genotype-Tissue Expression (GTEx), and Cancer Cell Line Encyclopedia (CCLE) databases were taken to examine the SNAI2 expression pattern in tissues and cancer cells. The link between SNAI2 gene expression levels and prognosis, as well as immune cell infiltration, was investigated using the Kaplan-Meier technique and Spearman correlation analysis. We also explored the expression and distribution of SNAI2 in various tumor tissues and cells by the THPA (Human Protein Atlas) database. We further investigated the relationship between SNAI2 expression levels and immunotherapy response in various clinical immunotherapy cohorts. Finally, the immunoblot was used to quantify the SNAI2 expression levels, and the proliferative and invasive ability of pancreatic cancer cells was determined by colony formation and transwell assays.ResultsWe discovered heterogeneity in SNAI2 expression in different tumor tissues and cancer cell lines by exploring public datasets. The genomic alteration of SNAI2 existed in most cancers. Also, SNAI2 exhibits prognosis predictive ability in various cancers. SNAI2 was significantly correlated with immune-activated hallmarks, cancer immune cell infiltrations, and immunoregulators. It’s worth noting that SNAI2 expression is significantly related to the effectiveness of clinical immunotherapy. SNAI2 expression was also found to have a high correlation with the DNA mismatch repair (MMR) genes and DNA methylation in many cancers. Finally, the knockdown of SNAI2 significantly weakened the proliferative and invasive ability of pancreatic cancer cells.ConclusionThese findings suggested that SNAI2 could be used as a biomarker in human pan-cancer to detect immune infiltration and poor prognosis, which provides a new idea for cancer treatment.

BackgroundIt has been well acknowledged that disordered intestinal microflora and their fermented products play crucial role during the development of hypertension (HTN). Aberrant profiles of fecal bacteria have been documented in subjects with isolated systolic HTN (ISH) and isolated diastolic HTN (IDH) previously. Nevertheless, evidence regarding the association of metabolic products in the bloodstream with ISH, IDH and combined systolic and diastolic HTN (SDH) remains scarce.MethodsWe performed a cross-sectional study and conducted untargeted liquid chromatography-mass spectrometry (LC/MS) analysis on serum samples of 119 participants, including 13 subjects with normotension (SBP

IntroductionPromoting the development of digital technology is an important step in meeting the challenge of global climate change and achieving carbon peaking and carbon neutrality goals.MethodsBased on panel data of Chinese cities from 2006 to 2020, this paper used econometrics to investigate the impact and mechanism of digital technology on carbon emissions.ResultsThe results showed that digital technology can significantly reduce carbon emission intensity and improve carbon emission efficiency. These results remained robust after changing the estimation method, adding policy omission variables, replacing core variables, and solving the endogeneity problem. Digital technology can indirectly reduce carbon emissions by promoting green technological innovation and reducing energy intensity, and it plays a significant role in the carbon emission reduction practices of carbon emission trading policies and comprehensive national big data pilot zones. The replicability, non-exclusivity, and high mobility of digital technology help to accelerate the spread of knowledge and information between different cities, which leads to a spillover effect on carbon emission reductions. Our unconditional quantile regression model results showed that digital technology’s carbon emission reduction effect continuously decreases with increases in carbon dioxide emissions.DiscussionThe results of this paper provide evidence for the potential use of digital technology in achieving the goal of carbon neutrality, which is of great significance for achieving high-quality innovation and promoting the green transformation of the economy and society.

The gastrointestinal tract contains a complex microbial community. Peyer’s patches (PPs) play an important role in inducing mucosal immune responses in the gastrointestinal tract. However, little is known about the effect of commensal microbiota on the host’s PPs. Here, we analyzed the phenotypic-to-transcriptome changes in the intestine PPs of specific pathogen-free (SPF) and germ-free (GF) piglets (fed in an environment with and without commensal microbiota, respectively) to elucidate the role of commensal microbiota in host intestine mucosal immunity. Analyses of anatomical and histological characteristics showed that commensal microbiota deficiency led to PP hypoplasia, especially regarding B and T cells. A total of 12,444 mRNAs were expressed in 12 libraries; 2,156 and 425 differentially expressed (DE) mRNAs were detected in the jejunal PP (JPP) and ileal PP (IPP), respectively (SPF vs. GF). The shared DE mRNAs of the JPP and IPP were mainly involved in basic physiological and metabolic processes, while the specific DE mRNAs were enriched in regulating immune cells in the JPP and microbial responses and cellular immunity in the IPP. Commensal microbiota significantly modulated the expression of genes related to B-cell functions, including activation, proliferation, differentiation, apoptosis, receptor signaling, germinal center formation, and IgA isotype class switching, particularly in the JPP. TLR4 pathway-related genes were induced in response to microbial colonization and in LPS/SCFA-treated B cells. We also detected 69 and 21 DE lncRNAs in the JPP and IPP, respectively, and four one-to-one lncRNA-mRNA pairs were identified. These findings might represent key regulatory axes for host intestine mucosal immunity development during microbial colonization. Overall, the findings of this study revealed that commensal microbiota modulated phenotypic characteristics and gene expression in the piglet intestine PPs and underscored the importance of early microbial colonization for host mucosal immunity development.

Glioblastoma multiforme (GBM) is a brain tumor with high mortality and recurrence rate. Radiotherapy and chemotherapy after surgery are the main treatment options available for GBM. However, patients with glioblastoma have a grave prognosis. The major reason is that most GBM patients are resistant to radiotherapy. UBA1 is considered an attractive potential anti-tumor therapeutic target and a key regulator of DNA double-strand break repair and genome replication in human cells. Therefore, we hypothesized that TAK-243, the first-in-class UBA1 inhibitor, might increase GBM sensitivity to radiation. The combined effect of TAK-243 and ionizing radiation on GBM cell proliferation, and colony formation ability was detected using CCK-8, colony formation, and EdU assays. The efficacy of TAK-243 combined with ionizing radiation for GBM was further evaluated in vivo, and the mechanism of TAK-243 sensitizing radiotherapy was preliminarily discussed. The results showed that TAK-243, in combination with ionizing radiation, significantly inhibited GBM cell proliferation, colony formation, cell cycle arrest in the G2/M phase, and increased the proportion of apoptosis. In addition, UBA1 inhibition by TAK-243 substantially increased the radiation-induced γ-H2AX expression and impaired the recruitment of the downstream effector molecule 53BP1. Therefore, TAK-243 inhibited the radiation-induced DNA double-strand break repair and thus inhibited the growth of GBM cells. Our results provided a new therapeutic strategy for improving the radiation sensitivity of GBM and laid a theoretical foundation and experimental basis for further clinical trials.

Background: Cigarette smoking is an important environmental risk factor for cardiovascular events of hypertension (HTN). Existing studies have provided evidence supporting altered gut microbiota by cigarette smoking, especially in hypertensive patients. Metabolic biomarkers play a central role in the functional potentials of the gut microbiome but are poorly characterized in hypertensive smokers. To explore whether serum metabolomics signatures and compositions of HTN patients were varied in smokers, and investigate their connecting relationship to gut microbiota, the serum metabolites were examined in untreated hypertensive patients using untargeted liquid chromatography-mass spectrometry (LC/MS) analysis.Results: A dramatic difference and clear separation in community features of circulating metabolomics members were seen in smoking HTN patients compared with the non-smoking controls, according to partial least squares discrimination analysis (PLS-DA) and orthogonal partial least squares discrimination analysis (OPLS-DA). Serum metabolic profiles and compositions of smoking patients with HTN were significantly distinct from the controls, and were characterized by enrichment of 12-HETE, 7-Ketodeoxycholic acid, Serotonin, N-Stearoyl tyrosine and Deoxycholic acid glycine conjugate, and the depletion of Tetradecanedioic acid, Hippuric acid, Glyceric acid, 20-Hydroxyeicosatetraenoic acid, Phenylpyruvic acid and Capric acid. Additionally, the metabolome displayed prominent functional signatures, with a majority proportion of the metabolites identified to be discriminating between groups distributed in Starch and sucrose metabolism, Caffeine metabolism, Pyruvate metabolism, Glycine, serine and threonine metabolism, and Phenylalanine metabolic pathways. Furthermore, the observation of alterations in metabolites associated with intestinal microbial taxonomy indicated that these metabolic members might mediate the effects of gut microbiome on the smoking host. Indeed, the metabolites specific to smoking HTNs were strongly organized into co-abundance networks, interacting with an array of clinical parameters, including uric acid (UA), low-denstiy lipoprotein cholesterol (LDLC) and smoking index.Conclusions: In conclusion, we demonstrated disparate circulating blood metabolome composition and functional potentials in hypertensive smokers, showing a linkage between specific metabolites in blood and the gut microbiome.

As an integration of artificial intelligence and advanced manufacturing technology, intelligent manufacturing has realized the innovation of manufacturing mode and created conditions for the green development of industry. After constructing a theoretical framework between intelligent manufacturing and industrial green total factor productivity, this paper uses panel data of 30 provinces in China from 2006 to 2020, and expresses the level of intelligent manufacturing with industrial robot density, to discuss the economic effects and mechanisms of intelligent manufacturing. The results show that intelligent manufacturing has a positive effect on industrial green total factor productivity, and the panel quantile regression model indicates that there is an increasing marginal effect. With the quantile points going from low to high, the coefficient and statistical significance become larger. Human capital is the mechanism for intelligent manufacturing to improve industrial green total factor productivity. Green technology innovation and producer service industry agglomeration have strengthened the positive effect. There is also heterogeneity in the effect, and the stronger the effect in regions launched local pilot schemes for carbon emissions trading and industrial green transformation development policy. In order to give full play to the technological dividend and empower sustainable industrial development, the paper argues that we need to accelerate the integration of artificial intelligence and manufacturing technology, thus improving the level of industrial intelligence and empowering green development.

Purpose: To develop predictive models for the intraocular pressure (IOP) of patients undergoing small incision lenticule extraction (SMILE) procedures, measured with a noncontact tonometer (NCT), Goldmann applanation tonometry (GAT), and an ocular response analyzer (ORA).Methods: In this prospective study, a total of 104 eyes (−6.23 ± 2.06 diopters) of 52 patients (24.38 ± 4.76 years) undergoing SMILE procedures were included. The intraocular pressure was measured (IOPNCT with NCT, IOPGAT with GAT, and IOPcc and IOPg with ORA) before surgery and at postoperative 6 months. Information on age, preoperative and attempted spherical equivalent (SE), ablation depth, preoperative values and postoperative changes in central corneal thickness (CCT), K1, K2, Km, corneal hysteresis (CH) and corneal resistance factor (CRF) values was collected in order to predict IOPs.Results: All surgeries were uneventful. At postoperative 6 months, the efficacy and safety index were 1.04 ± 0.15 and 1.08 ± 0.18, respectively. Significant decreases were detected in postoperative IOPNCT, IOPGAT, IOPcc, and IOPg compared to preoperative values (all p < 0.001). No relationship was found between any IOP and ablation depth, attempted SE, and preoperative SE, as well as CCTdifference (all p > 0.05). Predictive models for IOPs were constructed to predict preoperative values, and R2 values were 67.5% (IOPNCT), 64.5% (IOPGAT), 78.7% (IOPcc), and 82.0% (IOPg). The prediction band of IOPNCT and IOPGAT was 7.4–15.1 mmHg and 8–16 mmHg, respectively.Conclusion: Predictive models for IOP measurements after SMILE procedures can be helpful in clinical practice.

Bromine-rich lithium argyrodite electrolytes with high ionic conductivity and low cost are promising for the replacement of flammable liquid electrolytes and separators in lithium-ion batteries. However, the synthesis process of argyrodite electrolytes is usually complex and time-consuming. We use a facile solid-state reaction method to obtain a highly Li-ion conductive Li5.5PS4.5Br1.5 (LPSB). The influence of annealing temperature on the phase and ionic conductivity of the LPSB was investigated for the first time. High ionic conductivity of 5.21 × 10−3 S cm−1 at room temperature for the LPSB with minor LiBr impurity was achieved by direct annealing at 430°C for 8 h. The In/InLi | LPSB | LiCoO2@ LiNb0.5Ta0.5O3 (LCO(coated))-LPSB cell with 8.53 mg cm−2 LCO loading shows a discharge capacity of 102 mAh g−1 with high-capacity retention of 93% after 70 cycles at 0.5 mA cm−2 at 30°C.

Porcine reproductive and respiratory syndrome virus (PRRSV) is a highly contagious disease that affects the global pig industry. To understand mechanisms of susceptibility/resistance to PRRSV, this study profiled the time-serial white blood cells transcriptomic and serum metabolomic responses to PRRSV in piglets from a crossbred population of PRRSV-resistant Tongcheng pigs and PRRSV-susceptible Large White pigs. Gene set enrichment analysis (GSEA) illustrated that PRRSV infection up-regulated the expression levels of marker genes of dendritic cells, monocytes and neutrophils and inflammatory response, but down-regulated T cells, B cells and NK cells markers. CIBERSORT analysis confirmed the higher T cells proportion in resistant pigs during PRRSV infection. Resistant pigs showed a significantly higher level of T cell activation and lower expression levels of monocyte surface signatures post infection than susceptible pigs, corresponding to more severe suppression of T cell immunity and inflammatory response in susceptible pigs. Differentially expressed genes between resistant/susceptible pigs during the course of infection were significantly enriched in oxidative stress, innate immunity and humoral immunity, cell cycle, biotic stimulated cellular response, wounding response and behavior related pathways. Fourteen of these genes were distributed in 5 different QTL regions associated with PRRSV-related traits. Chemokine CXCL10 levels post PRRSV infection were differentially expressed between resistant pigs and susceptible pigs and can be a promising marker for susceptibility/resistance to PRRSV. Furthermore, the metabolomics dataset indicated differences in amino acid pathways and lipid metabolism between pre-infection/post-infection and resistant/susceptible pigs. The majority of metabolites levels were also down-regulated after PRRSV infection and were significantly positively correlated to the expression levels of marker genes in adaptive immune response. The integration of transcriptome and metabolome revealed concerted molecular events triggered by the infection, notably involving inflammatory response, adaptive immunity and G protein-coupled receptor downstream signaling. This study has increased our knowledge of the immune response differences induced by PRRSV infection and susceptibility differences at the transcriptomic and metabolomic levels, providing the basis for the PRRSV resistance mechanism and effective PRRS control.

Detailed insight into the radiation-induced changes in tumor microvasculature is crucial to maximize the efficacy of radiotherapy against breast cancer. Recent advances in imaging have enabled precise targeting of solid lesions. However, intratumoral heterogeneity makes treatment planning and monitoring more challenging. Conventional imaging cannot provide high-resolution observation and longitudinal monitoring of large-scale microvascular in response to radiotherapy directly in deep tissues. Herein, we report on an emerging non-invasive imaging assessment method of morphological and functional tumor microvasculature responses with high spatio-temporal resolution by means of optoacoustic imaging (OAI). In vivo imaging of 4T1 breast tumor response to a conventional fractionated radiotherapy at varying dose (14 × 2 Gy and 3 × 8 Gy) has been performed after 2 weeks following treatment. Remarkably, optoacoustic images can generate richful contrast for the tumor microvascular architecture. Besides, the functional status of tumor microvasculature and tumor oxygenation levels were further estimated using OAI. The results revealed the differential (size-dependent) nature of vascular responses to radiation treatments at varying doses. The vessels exhibited an decrease in their density accompanied by a decline in the number of vascular segments following irradiation, compared to the control group. The measurements further revealed an increase of tumor oxygenation levels for 14 × 2 Gy and 3 × 8 Gy irradiations. Our results suggest that OAI could be used to assess the response to radiotherapy based on changes in the functional and morphological status of tumor microvasculature, which are closely linked to the intratumor microenvironment. OAI assessment of the tumor microenvironment such as oxygenation status has the potential to be applied to precise radiotherapy strategy.

Background/aimsNon-alcoholic fatty liver disease (NAFLD) is one of the most common liver diseases worldwide. Iron overload has been implicated in chronic non-communicable liver diseases, but its relationship with NAFLD remains unclear. This study aimed to investigate the underlying roles of iron overload in the development of NAFLD.MethodsMale Sprague Dawley rats were fed with a high-fat diet (HFD) and/or iron for 8, 12, and 20 weeks. Some rats fed with HFD plus iron also received intraperitoneal injection of deferoxamine (DFO) for 8 weeks. Liver steatosis, lipid metabolism and injury were evaluated.ResultsA NAFLD model, including typical liver steatosis, was established by feeding rats with a HFD, while iron overload alone is not enough to induce severe NAFL. Compared with rats fed a HFD, excess iron further increased lipid accumulation, serum levels of lipids, enzymes of liver function, and expression levels of CD36 and FAS in rat liver. In addition, iron overload decreased the activities of antioxidative enzymes in liver compared with HFD rats. The levels of CPT1 and the ratios of p-ACC/ACC were also decreased by iron overload. DFO effectively reversed the abnormal lipid metabolism and liver damage induced by a high-fat, high-iron diet.ConclusionA HFD plus iron overload might synergistically aggravate lipid metabolism disorders, liver injury, and oxidative damage, compared with a HFD alone. DFO might help to alleviate lipid metabolism dysfunction and improve the pathogenesis of NAFLD.

ObjectiveTo study the efficacy of interval debulking surgery (IDS) plus hyperthermic intraperitoneal chemotherapy (HIPEC) compared to IDS alone for the treatment of ovarian cancer after neoadjuvant chemotherapy (NACT).MethodsWe conducted a retrospective study of patients with stage IIIC/IV high-grade serous ovarian carcinoma who underwent surgery at our center from January 2018 to December 2019. Patients who underwent IDS after NACT with (N = 20) or without (N = 42) HIPEC were included. HIPEC was administered after surgery and was combined with 1–2 courses of intraperitoneal hyperthermic perfusion with normal saline only. We analyzed clinical information and outcomes for the two groups.ResultsThe median progression-free survival (PFS) was 14.05 months in the IDS plus HIPEC group and 12.97 months in the IDS group (P = 0.597). The median overall survival (OS) was not reached. After adjustment for age between the two groups, the differences in PFS and OS remained nonsignificant. The change ratio of postoperative CA-125 to preoperative CA-125 was 0.66 in the IDS plus HIPEC group and 0.53 in the IDS group (P = 0.341). The difference in human epididymis protein 4 (HE-4) change ratio between the two groups was nonsignificant (P = 0.225). No significant difference was observed in the occurrence of grade 3 and 4 adverse events between the two groups (P = 0.201).ConclusionAfter NACT, IDS plus HIPEC did not show significant PFS and tumor index change ratio benefits over IDS alone in patients with primary ovarian cancer. Further investigations are needed to assess the role of HIPEC in the treatment of ovarian cancer.

PurposeTo investigate long-term trends in corneal densitometry and associated influencing factors following small incision lenticule extraction (SMILE).MethodsA comparative study was performed among 72 eyes of 38 patients undergoing SMILE. Eyes were divided into moderate myopia [mean spherical equivalent (SE),−4.22 ± 0.68D] and high myopia (mean SE,−7.63 ± 1.09 D) groups. Visual acuity, manifest refraction, corneal topography and corneal densitometry (CD) were evaluated preoperatively and 3 years postoperatively.ResultsThe efficacy indices at last postoperative follow-up (42.47 ± 0.51 months) were 0.92 ± 0.21 and 0.97 ± 0.22, the safety indices were 1.12 ± 0.17 and 1.14 ± 0.21 for high and moderate myopia, respectively (all P > 0.05). CD values in the 0–6 mm zone of the posterior corneal layer was statistically significantly lower than the preoperative values in both groups. Postoperative CD values (0–2 mm zone) in the posterior layer of the high myopia group were statistically significantly lower than in the moderate myopia group (P = 0.025); CD values (2–6 mm zone) in the anterior layer were higher in the high myopia group (P = 0.026). Correlation analyses showed that CD values in the 0–2 mm middle layer were negatively correlated with lenticule thickness in high myopia (r = −0.411, P = 0.016); there was a negative correlation between the CD values (0–6 mm) and corneal oblique trefoil in this group (P < 0.05).ConclusionCorneal transparency in the 0–6 mm zone of the posterior cornea increased following SMILE in moderate and high myopia. Long-term CD values in high myopia may be correlated with oblique trefoil and lenticule thickness.

In the airway, IgE is traditionally regarded as a key mediator in allergic diseases, such as AR and allergic asthma. However, growing evidence demonstrates the importance of local IgE in airway inflammatory diseases, irrespective of the presence of allergy. In this review, we discuss the most recent evidence for IgE in chronic rhinosinusitis with nasal polyps(CRSwNP), including the local IgE’s characteristics, the modulation of its synthesis, and its function. The levels of local IgE are significantly elevated in polyps independently of IgE serum levels and atopic status. Local IgE, which is correlated with type 2 inflammation, is polyclonal and functional. IgE is produced by active B cells and is dependent on the class switch recombination(CSR). In NPs, this process is triggered by not only allergens but also microbial colonization, especially the superantigen- Staphylococcus aureus. The production of local IgE is modulated by lymphocytes(such as Tfh, ILC2s, iTreg), cytokines(such as IL-4, IL-13, IFN-γ, TGF-β, IL-2, IL-21), transcription factors, and B cell-intrinsic factor. Due to the central role of IgE in NPs, it is regarded as an ideal target for therapy and has been proved to be clinically successful. Based on this knowledge, we believe that exploring the trigger and regulatory factors for the activation of local B cells and CSR to IgE will provide more valuable information for us to recognize the pathological mechanisms of local IgE and offer the possible option for new therapeutic targets of nasal polyps.

PurposeTo analyze the development process of small incision lenticule extraction (SMILE) surgery in a 12-year period.MethodsWe conducted a literature search for SMILE research from 2011 to 2022 using the Science Citation Index Expanded (SCIE) of the Web of Science Core Collection (WoSCC). The VOS viewer, and CiteSpace software were used to perform the bibliometric analysis. Publication language, annual growth trend, countries/regions and institutions, journals, keywords, references, and citation bursts were analyzed.ResultsA total of 731 publications from 2011 to 2022 were retrieved. Annual publication records grew from two to more than 100 during this period. China had the highest number of publications (n = 326). Sixty-five keywords that appeared more than four times were classified into six clusters: femtosecond laser technology, dry eye, biomechanics, visual quality, complications, and hyperopia.ConclusionThe number of literatures has been growing rapidly in the past 12 years. Our study provides a deep insight into publications on SMILE for researchers and clinicians with bibliometric analysis for the first time.

ZnO/Graphene (G)/Graphene Oxide (GO)/Multi-walled Carbon Nanotube (MCNT) composite aerogels with a three-dimensional porous structure were prepared by the sol-gel method under average temperature and alkaline conditions, combined with freeze-drying process and heat treatment process. The photocatalytic degradation of Rhodamine B (RhB) was mainly studied. The scanning electron microscope (SEM) test results showed that the morphology uniformity of the ZnO/G/GO/MCNT composite aerogel was significantly enhanced, which effectively solving the agglomeration problem of MCNT and ZnO. The photocatalytic degradation test results of RhB show that due to the synergistic effect of physical adsorption and photocatalytic degradation, the total degradation efficiency of RhB by ZnO/G/GO/MCNT could reach 86.8%, which is 3.3 times higher than that of ZnO. In addition, the synergistic effect of ZnO and G effectively hinders the recombination of photo-generated electron-hole pairs and enhances photocatalytic activity. The ZnO/G/GO/MCNT composite aerogel can be applied in the visible light catalytic degradation of water pollution.

Thrombotic complications pose serious health risks worldwide. A significant change in our understanding of the pathophysiology of thrombosis has occurred since the discovery of extracellular traps (ETs) and their prothrombotic properties. As a result of immune cells decondensing chromatin into extracellular fibers, ETs promote thrombus formation by acting as a scaffold that activates platelets and coagulates them. The involvement of ETs in thrombosis has been reported in various thrombotic conditions including deep vein thrombosis (DVT), pulmonary emboli, acute myocardial infarction, aucte ischemic stroke, and abdominal aortic aneurysms. This review summarizes the existing evidence of ETs in human and animal model thrombi. The authors described studies showing the existence of ETs in venous or arterial thrombi. In addition, we studied potential novel therapeutic opportunities related to the resolution or prevention of thrombosis by targeting ETs.

Lactic acid bacteria (LAB) have already been used as fermentation strains to enhance the antioxidant capacity of polyphenols. Antioxidant capacity is one of the most important factors to inhibit advanced glycation end product (AGE) formation and could LAB increase the inhibitory capacity of procyanidins on AGEs formation? It was surprising that opposite results were obtained both in simulated food processing and gastrointestinal digestion systems. After incubation with Lactobacillus plantarum (L. plantarum), litchi pericarp oligomeric procyanidins (LPOPCs) were bioconverted to several phenolic acids, which increased the antioxidant activity as expected. However, antiglycation ability and trapping carbonyl compounds capacity both weakened and it might be the primary reason for decreasing the inhibitory effect on AGE formation. Furthermore, it was found that LPOPCs incubated with L. plantarum inhibited the activity of digestive enzymes and thus decreased the digestibility of glycated protein. Our study systematically proposed for the first time that procyanidins bioconversion is an effective means to improve the antioxidant activity but has no remarkable promoting effect on AGEs inhibition.

Magnesium (Mg)-based materials are considered as potential materials for biodegradable vascular stents, and some Mg-based stents have obtained regulatory approval. However, the development and application of Mg-based stents are still restricted by the rapid degradation rate of Mg and its alloys. In order to screen out the desirable Mg-based materials for stents, the degradation behavior still needs further systematic study, especially the degradation behavior under the action of near-physiological fluid. Currently, the commonly used Mg-based vascular stent materials include pure Mg, AZ31, and WE43. In this study, we systematically evaluated their corrosion behaviors in a dynamic environment and studied the effect of their degradation products on the behavior of vascular cells. The results revealed that the corrosion rate of different Mg-based materials was related to the composition of the elements. The dynamic environment accelerated the corrosion of Mg-based materials. All the same, AZ31 still shows good corrosion resistance. The effect of corrosive products on vascular cells was beneficial to re-endothelialization and inhibition of smooth muscle cell proliferation at the implantation site of vascular stent materials.

Cancer-associated fibroblasts (CAFs) are a major contributor to tumor stromal crosstalk in the tumor microenvironment (TME) and boost tumor progression by promoting angiogenesis and lymphangiogenesis. This study aimed to identify prognostic genes associated with CAFs that lead to high morbidity and mortality in ovarian cancer (OC) patients. We performed bioinformatics analysis in 16 multicenter studies (2,742 patients) and identified CAF-associated hub genes using the weighted gene co-expression network analysis (WGCNA). A machine learning methodology was used to identify COL16A1, COL5A2, GREM1, LUM, SRPX, and TIMP3 and construct a prognostic signature. Subsequently, a series of bioinformatics algorithms indicated risk stratification based on the above signature, suggesting that high-risk patients have a worse prognosis, weaker immune response, and lower tumor mutational burden (TMB) status but may be more sensitive to routine chemotherapeutic agents. Finally, we characterized prognostic markers using cell lines, immunohistochemistry, and single-cell sequencing. In conclusion, these results suggest that the CAF-related signature may be a novel pretreatment guide for anti-CAFs, and prognostic markers in CAFs may be potential therapeutic targets to inhibit OC progression.

ObjectiveGynecological malignant tumor patients with hypertension, even if blood pressure is well controlled, are prone to hypertension before surgery. We plan to verify the effect of transcutaneous electrical acupoint stimulation (TEAS) on stabilizing blood pressure before operation.MethodsWe enrolled 91 patients and randomly divided them into TEAS group (n=46) and control group (n=45). Patients in TEAS group received TEAS at acupoints Hegu and Neiguan. Patients in control group received transcutaneous electrical stimulation at the nonacupoint position of the upper limbs. After entering the operating room, the blood pressure before and after induction was measured. The main results were the occurrence of preinduction hypertension and postinduction hypotension.ResultsThere was no difference in the general information of the two groups. There were four cases (9%) of preinduction hypertension in TEAS group and 13 cases (29%) in control group. The incidence in TEAS group was significantly lower (P=0.013). There were five cases (11%) of postinduction hypotension in TEAS group and eight cases (18%) in control group. There was no significant difference between the two groups (P=0.346). The systolic blood pressure (SBP), diastolic blood pressure (DBP) and mean blood pressure (MBP) of the highest blood pressure before induction in TEAS group were lower than those in control group (P=0.002, 0.002, and 0.001). There was no difference in SBP, DBP, or MBP between the two groups on the day before the operation. There was no difference in the lowest blood pressure before operation between the two groups after inductionConclusionTEAS can prevent preinduction hypertension in patients with gynecological malignant tumors.Clinical Trial Registrationhttp://www.chictr.org.cn/showproj.aspx?proj=143276, identifier ChiCTR2100054336.

2D ZnO is one of the most attractive materials for potential applications in photocatalysis, gas and light detection, ultraviolet light-emitting diodes, resistive memory, and pressure-sensitive devices. The electronic structures, magnetic properties, and optical properties of M (Li, Na, Mg, Ca, or Ga) and TM (Cr, Co, Cu, Ag, or Au) adsorbed g-ZnO were investigated with density functional theory (DFT). It is found that the band structure, charge density difference, electron spin density, work function, and absorption spectrum of g-ZnO can be tuned by adsorbing M or TM atoms. More specifically, the specific charge transfer occurs between g-ZnO and adsorbed atom, indicating the formation of a covalent bond. The work functions of M adsorbed g-ZnO systems are obviously smaller than that of intrinsic g-ZnO, implying great potential in high-efficiency field emission devices. The Li, Na, Mg, Ca, Ga, Ag, or Au adsorbed g-ZnO systems, the Cr adsorbed g-ZnO system, and the Co or Cu adsorbed g-ZnO systems exhibit non-magnetic semiconductor proprieties, magnetic semiconductor proprieties, and magnetic metal proprieties, respectively. In addition, the magnetic moments of Cr, Co, or Cu adsorbed g-ZnO systems are 4 μB, 3 μB, or 1 μB, respectively, which are mainly derived from adsorbed atoms, suggesting potential applications in nano-scale spintronics devices. Compared with the TM absorbed g-ZnO systems, the M adsorbed g-ZnO systems have more obvious absorption peaks for visible light, particularly for Mg or Ca adsorbed g-ZnO systems. Their absorption peaks appear in the near-infrared region, suggesting great potential in solar photocatalysis. Our work contributes to the design and fabrication of high-efficiency field emission devices, nano-scale spintronics devices, and visible-light responsive photocatalytic materials.

PurposeIt is well-known that the pathological complete response (pCR) rate in patients with luminal A cancer (LAC) is lower than those of other subtypes of breast cancer. The phenotype of cancer often alters after neoadjuvant chemotherapy (NAC) which may be related to hypoxia, and the latter might induce the drift of the estrogen receptor (ER). The phenotype drift in local advanced LAC after NAC might influence the long-term prognosis.MethodsThe oxygen concentration of cancer tissues during NAC was recorded and analyzed (n = 43). The expression of ER and claudin-6 was detected in pre- and post-NAC specimens.ResultsNAC might induce the cycling intracanceral hypoxia, and the pattern was related to NAC response. The median follow-up time was 61 months. Most of the patients (67%) with stable or increased ER and claudin-6 expression exhibited perfect prognosis (DFS = 100%, 61 months). About 20% of patients with decreased claudin-6 would undergo the poor prognosis (DFS = 22.2%, 61 months). The contrasting prognosis (100% vs. 22.2%) had nothing to do with the response of NAC in the above patients. Only 13% patients had stable claudin-6 and decreased ER, whose prognosis might relate to the response of NAC.ConclusionNAC might induce cycling intracanceral hypoxia to promote the phenotype drift in local advanced LAC, and the changes in ER and claudin-6 after NAC would determine the long-term prognosis.

The human gut microbiota play essential roles in metabolism and human health, especially by enzymatically utilizing dietary fiber that the host cannot directly digest and releasing functional components including short-chain fatty acids (SCFAs) and hydroxycinnamic acids (e.g., ferulic acid). In our previous study, seven potential feruloyl esterase (FAE) genes were identified from the gut microbiota. In the current work, one of the genes encoding a novel FAE (DfFAE) from Dorea formicigenerans of Firmicutes was bacterially expressed, purified and characterized. The 30.5 kDa type-A DfFAE has an optimum pH and temperature of 8.4 and 40 °C, respectively, exhibiting a higher substrate specificity toward short-chain acyl-ester substrate (pNPA). The AlphaFold2 based ab initio structural modeling revealed a five α-helices cap domain that shaped an unusually narrow and deep active site pocket containing a specific substrate access tunnel in DfFAE. Furthermore, rational design strategy was subjected to the active site pocket in an aim of improving its enzymatic activities. The mutants V252A, N156A, W255A, P149A, and P186A showed 1.8 to 5.7-fold increase in catalytic efficiency toward pNPA, while W255A also exhibited altered substrate preference toward long-chain substrate pNPO (45.5-fold). This study highlighted an unusual active site architecture in DfFAE that influenced its substrate selectivity and illustrated the applicability of rational design for enhanced enzymatic properties.

PurposeTo evaluate the influence of the origin of astigmatism on the correction of myopic astigmatism by toric implantable collamer lens (TICL) and compare it with femtosecond laser small incision lenticule extraction (SMILE).MethodsOcular residual astigmatism (ORA) was determined by vector analysis using manifest refraction and Scheimpflug camera imaging of the anterior cornea. One-to-one matching between the TICL and SMILE groups was performed by preoperative manifest refractive astigmatism (RA) and ORA, tolerating a maximum difference of 0.50 diopter (D) for RA and 0.25 D for ORA. Patients of each group were further divided into groups according to ORA (high > 1.0 D; low ≤ 1.0 D). The baseline and 12-month postoperative data were analyzed. Data are expressed as mean ± standard deviation (SD). A value of p less than 0.05 was considered statistically significant.ResultsFor the TICL group, no significant differences in the postoperative RA, safety index, efficacy index, index of success (IOS), correction index (CI), and angle of error (AOE) were found between high (n = 36) and low ORA (n = 36) groups (Mann–Whitney U test, p > 0.05). For the SMILE group, the postoperative RA (high: −0.67 ± 0.43 D, low: −0.39 ± 0.29 D, Mann–Whitney U test, p = 0.003) and IOS (high: 0.50 ± 0.43, low: 0.25 ± 0.23, Mann–Whitney U test, p = 0.003) were greater in the high ORA group. When comparing TICL and SMILE groups, the mean postoperative RA (TICL: −0.48 ± 0.29 D, SMILE: −0.67 ± 0.43 D, Mann–Whitney U test, p = 0.03) and IOS (TICL: 0.32 ± 0.23, SMILE: 0.50 ± 0.43, Mann–Whitney U test, p = 0.03) were significantly higher in the SMILE group when the ORA was >1.0 D.ConclusionBoth TICL and SMILE are effective in correcting myopic astigmatism. ORA has a lesser effect on TICL than on SMILE.

Asymmetric septate uterus, commonly known as Robert’s uterus, is an exceedingly rare uterine malformation described for the first time in 1970 by Robert H. Currently, surgery is the therapy of choice for Robert’s uterus, with surgical choices ranging from laparotomy to minimally invasive surgery. In this paper, we reported that a 14-year-old girl with primary dysmenorrhea that gradually worsened three months after menarche had surgery after many imaging evaluations, and that the intraoperative diagnosis was Robert’s uterus. The diagnostic and therapeutic laparo-endoscopic single site(LESS) combined with hysteroscopy surgery for Robert’s uterine abnormality was shown via a step-by-step presentation of the method accompanied by narrated video footage. During the ten-month postoperative follow-up period, the patient had monthly recurrences with normal menstrual volume and no dysmenorrhea, demonstrating that as a minimally invasive treatment, LESS combined with hysteroscopy surgery is a successful methodfor diagnosing and treating this specific malformation.

The aquaculture industry is vital in providing a valuable protein food source for humans, but generates a huge amount of solid and dissolved wastes that pose great risks to the environment and aquaculture sustainability. Suspended solids (in short SS), one of the aquaculture wastes, are very difficult to be treated due to their high organic contents. The bioconversion from wastewater, food effluents, and activated sludge into poly-β-hydroxybutyrate (PHB) is a sustainable alternative to generate an additional income and could be highly attractive to the agricultural and environmental management firms. However, little is known about its potential application in aquaculture wastes. In the present study, we first determined that 7.2% of SS was PHB. Then, the production of PHB was increased two-fold by the optimal fermentation conditions of wheat bran and microbial cocktails at a C/N ratio of 12. Also, the PHB-enriched SS showed a higher total ammonia nitrogen removal rate. Importantly, we further demonstrated that the PHB-enriched SS as a feed could promote fish growth and up-regulate the expression of the immune-related genes. Our study developed an eco-friendly and simple approach to transforming problematic SS wastes into PHB-enriched high-quality food for omnivorous fish, which will increase the usage efficiency of SS and provide a cheaper diet for aquatic animals.

Recent studies have indicated the critical influence of gut microbiota on the occurrence of obesity. There is a significant risk of obesity in people with schizophrenia. This work proposed that the disorder of gut microbiota in patients with schizophrenia was based on microbial enterotypes. Ninety-seven patients with schizophrenia and 69 matched health controls were eligible. The fresh feces of all the subjects were collected and used to complete 16S rRNA sequence. Statistical analysis was performed to identify the intestinal type of gut microbiota and analyze their potential effects on metabolic function. The patients with enterotype-P had a higher BMI than that of the others. Several differences in the gut microbes of enterotype-P were found between the patients and the controls. Proteobacteria and Firmicutes had significantly higher abundance in the patients’ group with enterotype-P. The Bacteroidetes had higher abundance in health controls with enterotype-P. Different metabolic pathways of the microbiota with the enterotype-P were identified in the subjects categorized in different BMI intervals. The schizophrenia patients had a significantly higher BMI than that of health controls. The patients with enterotype-P had a higher BMI. Therefore, the enterotype-P might have a critical influence on a variety of metabolic pathways to disturb the metabolism of glucose and lipid in human body.

Pathogenic Th17, featured by their production of pro-inflammatory cytokines, are considered as a key player in most autoimmune diseases. The transcriptome of them is obviously distinct from that of conventional regulatory Th17. However, chromatin accessibility of the two Th17 groups have not been comprehensively compared yet. Here, we found that their chromatin-accessible regions(ChARs) significantly correlated with the expression of related genes, indicating that they might engage in the regulation of these genes. Indeed, pathogenic Th17 specific ChARs (patho-ChARs) exhibited a significant distribution preference in TSS-proximal region. We further filtered the patho-ChARs based on their conservation among mammalians or their concordance with the expression of their related genes. In either situation, the filtered patho-ChARs also showed a preference for TSS-proximal region. Enrichment of expression concordant patho-ChARs related genes suggested that they might involve in the pathogenicity of Th17. Thus, we also examined all ChARs of patho-ChARs related genes, and defined an opening ChAR set according to their changes in the Th17 to Th1 conversion. Interestingly, these opening ChARs displayed a sequential accessibility change from TSS-proximal region to TSS-distal region. Meanwhile, a group of patho-TFs (transcription factors) were identified based on the appearance of their binding motifs in the opening ChARs. Consistently, some of them also displayed a similar preference for binding the TSS-proximal region. Single-cell transcriptome analysis further confirmed that these patho-TFs were involved in the generation of pathogenic Th17. Therefore, our results shed light on a new regulatory mechanism underlying the generation of pathogenic Th17, which is worth to be considered for autoimmune disease therapy.

Vascular calcification (VC) is a complex ectopic calcification process and an important indicator of increased risk for diabetes, atherosclerosis, chronic kidney disease, and other diseases. Therefore, clarifying the pathogenesis of VC is of great clinical significance. Numerous studies have shown that the onset and progression of VC are similar to bone formation. Members of the bone morphogenetic protein (BMP) family of proteins are considered key molecules in the progression of vascular calcification. BMP type I receptor A (BMPR1A) is a key receptor of BMP factors acting on the cell membrane, is widely expressed in various tissues and cells, and is an important “portal” for BMP to enter cells and exert their biological effect. In recent years, many discoveries have been made regarding the occurrence and treatment of ectopic ossification-related diseases involving BMP signaling targets. Studies have confirmed that BMPR1A is involved in osteogenic differentiation and that its high expression in vascular endothelial cells and smooth muscle cells can lead to vascular calcification. This article reviews the role of BMPR1A in vascular calcification and the possible underlying molecular mechanisms to provide clues for the clinical treatment of such diseases.