Search

Abstract Background Evidence suggests that insulin resistance (IR) is an autonomous risk factor for cardiovascular disease (CVD). Nevertheless, the association between estimated glucose disposal rate (eGDR), a novel indicator of IR, and incident CVD and mortality in chronic kidney disease (CKD) patients without diabetes remains uncertain. Methods The study included 19,906 participants from the UK Biobank who had an estimated glomerular filtration rate (eGFR)

Abstract Perioperative anesthetic management entails a multitude of decision-making processes within complex medical scenarios. These demand the continuous and dynamic execution of precise decisions which poses significant challenges. In the age of big data, the exponential growth in data volume from diverse sources has revolutionized many fields, including healthcare, finance, and marketing. Machine learning has emerged as a powerful tool for analyzing big data, enabling the handling of large datasets and uncovering intricate patterns and relationships. The application of big data and artificial intelligence algorithms is gradually being integrated, enabling effective task completion in various stages of perioperative management, including risk prediction, decision support, and auxiliary examination. Through in-depth analysis of big data, healthcare professionals can gain insights into patient prognoses. This review provides a comprehensive overview of the distinctive features of perioperative big data and its applications in anesthesia management during the perioperative period.

Abstract As a Brassica crop, Brassica napus typically has single flowers that contain four petals. The double-flower phenotype of rapeseed has been a desirable trait in China because of its potential commercial value in ornamental tourism. However, few double-flowered germplasms have been documented in B. napus, and knowledge of the underlying genes is limited. Here, B. napus D376 was characterized as a double-flowered strain that presented an average of 10.92 ± 1.40 petals and other normal floral organs. F1, F2 and BC1 populations were constructed by crossing D376 with a single-flowered line reciprocally. Genetic analysis revealed that the double-flower trait was a recessive trait controlled by multiple genes. To identify the key genes controlling the double-flower trait, bulk segregant analysis sequencing (BSA-seq) and RNA-seq analyses were conducted on F2 individual bulks with opposite extreme phenotypes. Through BSA-seq, one candidate interval was mapped at the region of chromosome C05: 14.56–16.17 Mb. GO and KEGG enrichment analyses revealed that the DEGs were significantly enriched in carbohydrate metabolic processes, notably starch and sucrose metabolism. Interestingly, five and thirty-six DEGs associated with floral development were significantly up- and down-regulated, respectively, in the double-flowered plants. A combined analysis of BSA-seq and RNA-seq data revealed that five genes were candidates associated with the double flower trait, and BnaC05.ERS2 was the most promising gene. These findings provide novel insights into the breeding of double-flowered varieties and lay a theoretical foundation for unveiling the molecular mechanisms of floral development in B. napus.

Abstract Background Cancer-associated fibroblasts (CAFs) are the prominent cell type in the tumor microenvironment (TME), and CAF subsets have been identified in various tumors. However, how CAFs spatially coordinate other cell populations within the liver TME to promote cancer progression remains unclear. Methods We combined multi-region proteomics (6 patients, 24 samples), 10X Genomics Visium spatial transcriptomics (11 patients, 25 samples), and multiplexed imaging (92 patients, 264 samples) technologies to decipher the expression heterogeneity, functional diversity, spatial distribution, colocalization, and interaction of fibroblasts. The newly identified CAF subpopulation was validated by cells isolated from 5 liver cancer patients and in vitro functional assays. Results We identified a liver CAF subpopulation, marked by the expression of COL1A2, COL4A1, COL4A2, CTGF, and FSTL1, and named F5-CAF. F5-CAF is preferentially located within and around tumor nests and colocalizes with cancer cells with higher stemness in hepatocellular carcinoma (HCC). Multiplexed staining of 92 patients and the bulk transcriptome of 371 patients demonstrated that the abundance of F5-CAFs in HCC was associated with a worse prognosis. Further in vitro experiments showed that F5-CAFs isolated from liver cancer patients can promote the proliferation and stemness of HCC cells. Conclusions We identified a CAF subpopulation F5-CAF in liver cancer, which is associated with cancer stemness and unfavorable prognosis. Our results provide potential mechanisms by which the CAF subset in the TME promotes the development of liver cancer by supporting the survival of cancer stem cells.

Abstract Background Accurate measurement of hemoglobin concentration is essential for various medical scenarios, including preoperative evaluations and determining blood loss. Traditional invasive methods are inconvenient and not suitable for rapid, point-of-care testing. Moreover, current models, due to their complex parameters, are not well-suited for mobile medical settings, which limits the ability to conduct frequent and rapid testing. This study aims to introduce a novel, compact, and efficient system that leverages deep learning and smartphone technology to accurately estimate hemoglobin levels, thereby facilitating rapid and accessible medical assessments. Methods The study employed a smartphone application to capture images of the eye, which were subsequently analyzed by a deep neural network trained on data from invasive blood test data. Specifically, the EGE-Unet model was utilized for eyelid segmentation, while the DHA(C3AE) model was employed for hemoglobin level prediction. The performance of the EGE-Unet was evaluated using statistical metrics including mean intersection over union (MIOU), F1 Score, accuracy, specificity, and sensitivity. The DHA(C3AE) model’s performance was assessed using mean absolute error (MAE), mean-square error (MSE), root mean square error (RMSE), and R^2. Results The EGE-Unet model demonstrated robust performance in eyelid segmentation, achieving an MIOU of 0.78, an F1 Score of 0.87, an accuracy of 0.97, a specificity of 0.98, and a sensitivity of 0.86. The DHA(C3AE) model for hemoglobin level prediction yielded promising outcomes with an MAE of 1.34, an MSE of 2.85, an RMSE of 1.69, and an R^2 of 0.34. The overall size of the model is modest at 1.08 M, with a computational complexity of 0.12 FLOPs (G). Conclusions This system presents a groundbreaking approach that eliminates the need for supplementary devices, providing a cost-effective, swift, and accurate method for healthcare professionals to enhance treatment planning and improve patient care in perioperative environments. The proposed system has the potential to enable frequent and rapid testing of hemoglobin levels, which can be particularly beneficial in mobile medical settings. Trial Registration The clinical trial was registered on the Chinese Clinical Trial Registry (No. ChiCTR2100044138) on 20/02/2021.

Runoff prediction plays a crucial role in hydropower generation and flood prevention, enhancing prediction accuracy in hydrology. This study proposes an extreme forecast index (EFI)-driven runoff prediction approach using stacking ensemble learning to improve prediction performance. EFI is introduced as an input into four machine learning models (Support Vector Regression, Multi-layer Perceptron, Gradient Boosting Decision Tree, and Ridge Regression) for runoff prediction with lead times of 24 h, 48 h, and 72 h. The stacking ensemble learning framework comprises four base-models and a meta-model, and model hyperparameters are re-optimized using the particle swarm optimization algorithm. The approach focuses on predicting the inflow processes of the Geheyan Reservoir in the Qing River using EFI and runoff time series. Results demonstrate that the EFI-runoff simulation can improve runoff prediction capability due to EFI’s higher sensitivity to observed runoff, and the proposed stacking ensemble learning model outperforms the individual model in predicting runoff with all lead times. The relative flood peak error, mean relative error, root mean square error, and Nash-Sutcliffe efficiency coefficient of the model’s one-day-ahead prediction are 7.987%, 22.421%, 632.871 m3/s, and 0.771, respectively. Therefore, this approach can be effectively utilized to improve accuracy in short-term runoff prediction applications.

Introduction: The early diagnosis of kidney injury in type 2 diabetes (T2DM) is important to prevent the long-term damaging effects of kidney loss and is decisive for patient outcomes. While SIRT2 is implicated in diabetes pathogenesis, its correlation with diabetic nephropathy remains unexplored. This study was designed to evaluate the association of urine SIRT2 levels with diabetic kidney injury, as well as potential underlying mechanisms. Methods: In T2DM patients, db/db mice, and high glucose plus palmitic acid treated HK2 cell models, ELISA, Immunoturbidimetry, Immunohistochemistry, Western blot, and Quantitative real-time polymerase chain reaction were used to detect SIRT2 levels and kidney damage. According to urinary albumin/creatinine ratio (UACR), 163 T2DM patients were divided into three groups. Spearman correlation analysis was used to investigate the relationship between urinary sirtuin2/creatinine ratio (USCR) and biomarkers of kidney injury. The influencing factors of albuminuria in T2DM patients were analyzed by logistic regression model. Results: In our findings, the Macro group exhibited the highest USCR levels as UACR increased. There was a positive association between USCR and UACR, α1-microglobulin/creatinine ratio (UαCR), β2-microglobulin/creatinine ratio (UβCR), and retinol-binding protein/creatinine ratio (URCR), with a negative correlation observed with eGFR. Logistic ordered multiclassification regression analysis, adjusting for confounding variables, confirmed that USCR remained a significant risk factor for the severity of albuminuria in T2DM patients. In the db/db mice kidney SIRT2 protein level increased significantly. Increased SIRT2 protein levels were also observed in renal tubular epithelial cells treated with high glucose plus palmitic acid. Moreover, SIRT2 promotes the expression of proinflammatory factors TNF-α and IL-6 by modulating the phosphorylation of p38 MAPK and p-JNK in renal tubular cells induced by high glucose and palmitic acid. Conclusion: Urinary SIRT2 is closely related to eGFR, renal tubule injury, and urinary albumin excretion in T2DM patients, which is expected to be an important indicator to comprehensively reflect renal injury.

BackgroundThe mpox pandemic has caused widespread public concern around the world. The spread of misinformation through the internet and social media could lead to an infodemic that poses challenges to mpox control. ObjectiveThis review aims to summarize mpox-related infodemiology studies to determine the characteristics, influence, prevention, and control measures of the mpox infodemic and propose prospects for future research. MethodsThe scoping review was conducted based on a structured 5-step methodological framework. A comprehensive search for mpox-related infodemiology studies was performed using PubMed, Web of Science, Embase, and Scopus, with searches completed by April 30, 2024. After study selection and data extraction, the main topics of the mpox infodemic were categorized and summarized in 4 aspects, including a trend analysis of online information search volume, content topics of mpox-related online posts and comments, emotional and sentiment characteristics of online content, and prevention and control measures for the mpox infodemic. ResultsA total of 1607 articles were retrieved from the databases according to the keywords, and 61 studies were included in the final analysis. After the World Health Organization’s declaration of an mpox public health emergency of international concern in July 2022, the number of related studies began growing rapidly. Google was the most widely used search engine platform (9/61, 15%), and Twitter was the most used social media app (32/61, 52%) for researchers. Researchers from 33 countries were concerned about mpox infodemic–related topics. Among them, the top 3 countries for article publication were the United States (27 studies), India (9 studies), and the United Kingdom (7 studies). Studies of online information search trends showed that mpox-related online search volume skyrocketed at the beginning of the mpox outbreak, especially when the World Health Organization provided important declarations. There was a large amount of misinformation with negative sentiment and discriminatory and hostile content against gay, bisexual, and other men who have sex with men. Given the characteristics of the mpox infodemic, the studies provided several positive prevention and control measures, including the timely and active publishing of professional, high-quality, and easy-to-understand information online; strengthening surveillance and early warning for the infodemic based on internet data; and taking measures to protect key populations from the harm of the mpox infodemic. ConclusionsThis comprehensive summary of evidence from previous mpox infodemiology studies is valuable for understanding the characteristics of the mpox infodemic and for formulating prevention and control measures. It is essential for researchers and policy makers to establish prediction and early warning approaches and targeted intervention methods for dealing with the mpox infodemic in the future.

BackgroundType VI secretion system (T6SS) is widely present in Gram-negative bacteria and directly mediates antagonistic prokaryote interactions. PAAR (proline-alanine-alanine-arginine repeats) proteins have been proven essential for T6SS-mediated secretion and target cell killing. Although PAAR proteins are commonly found in A. baumannii, their biological functions are not fully disclosed yet. In this study, we investigated the functions of a PAAR protein termed TagP (T6SS-associated-gene PAAR), encoded by the gene ACX60_RS09070 outside the core T6SS locus of A. baumannii strain ATCC 17978.MethodsIn this study, tagP null and complement A. baumannii ATCC 17978 strains were constructed. The influence of TagP on T6SS function was investigated through Hcp detection and bacterial competition assay; the influence on environmental fitness was studied through in vitro growth, biofilm formation assay, surface motility assay, survivability in various simulated environmental conditions; the influence on pathogenicity was explored through cell adhesion and invasion assays, intramacrophage survival assay, serum survival assay, and G. melonella Killing assays. Quantitative transcriptomic and proteomic analyses were utilized to observe the global impact of TagP on bacterial status.ResultsCompared with the wildtype strain, the tagP null mutant was impaired in several tested phenotypes such as surface motility, biofilm formation, tolerance to adverse environments, adherence to eukaryotic cells, endurance to serum complement killing, and virulence to Galleria melonella. Notably, although RNA-Seq and proteomics analysis revealed that many genes were significantly down-regulated in the tagP null mutant compared to the wildtype strain, there is no significant difference in their antagonistic abilities. We also found that Histone-like nucleoid structuring protein (H-NS) was significantly upregulated in the tagP null mutant at both mRNA and protein levels.ConclusionsThis study enriches our understanding of the biofunction of PAAR proteins in A. baumannii. The results indicates that TagP involved in a unique modulation of fitness and virulence control in A. baumannii, it is more than a classic PAAR protein involved in T6SS, while how TagP play roles in the fitness and virulence of A. baumannii needs further investigation to clarify.

Abstract Anemia (hemoglobin (Hb)

Abstract Background Epigenetic modifications that exhibit circadian oscillations also promote circadian oscillations of gene expression. Brassica napus is a heterozygous polyploid species that has undergone distant hybridization and genome doubling events and has a young and distinct species origin. Studies incorporating circadian rhythm analysis of epigenetic modifications can offer new insights into differences in diurnal oscillation behavior among subgenomes and the regulation of diverse expressions of homologous gene rhythms in biological clocks. Results In this study, we created a high-resolution and multioscillatory gene expression dataset, active histone modification (H3K4me3, H3K9ac), and RNAPII recruitment in Brassica napus. We also conducted the pioneering characterization of the diurnal rhythm of transcription and epigenetic modifications in an allopolyploid species. We compared the evolution of diurnal rhythms between subgenomes and observed that the Cn subgenome had higher diurnal oscillation activity in both transcription and active histone modifications than the An subgenome. Compared to the A subgenome in Brassica rapa, the An subgenome of Brassica napus displayed significant changes in diurnal oscillation characteristics of transcription. Homologous gene pairs exhibited a higher proportion of diurnal oscillation in transcription than subgenome-specific genes, attributed to higher chromatin accessibility and abundance of active epigenetic modification types. We found that the diurnal expression of homologous genes displayed diversity, and the redundancy of the circadian system resulted in extensive changes in the diurnal rhythm characteristics of clock genes after distant hybridization and genome duplication events. Epigenetic modifications influenced the differences in the diurnal rhythm of homologous gene expression, and the diurnal oscillation of homologous gene expression was affected by the combination of multiple histone modifications. Conclusions Herein, we presented, for the first time, a characterization of the diurnal rhythm characteristics of gene expression and its epigenetic modifications in an allopolyploid species. Our discoveries shed light on the epigenetic factors responsible for the diurnal oscillation activity imbalance between subgenomes and homologous genes’ rhythmic expression differences. The comprehensive time-series dataset we generated for gene expression and epigenetic modifications provides a valuable resource for future investigations into the regulatory mechanisms of protein-coding genes in Brassica napus.

The accuracy of long-term runoff models can be increased through the input of local weather variables and global climate indices. However, existing methods do not effectively extract important information from complex input factors across various temporal and spatial dimensions, thereby contributing to inaccurate predictions of long-term runoff. In this study, local–global–temporal attention mechanisms (LGTA) were proposed for capturing crucial information on global climate indices on monthly, annual, and interannual time scales. The graph attention network (GAT) was employed to extract geographical topological information of meteorological stations, based on remotely sensed elevation data. A long-term runoff prediction model was established based on long-short-term memory (LSTM) integrated with GAT and LGTA, referred to as GAT–LGTA–LSTM. The proposed model was compared to five comparative models (LGTA–LSTM, GAT–GTA–LSTM, GTA–LSTM, GAT–GA–LSTM, GA–LSTM). The models were applied to forecast the long-term runoff at Luning and Pingshan stations in China. The results indicated that the GAT–LGTA–LSTM model demonstrated the best forecasting performance among the comparative models. The Nash–Sutcliffe Efficiency (NSE) of GAT–LGTA–LSTM at the Luning and Pingshan stations reached 0.87 and 0.89, respectively. Compared to the GA–LSTM benchmark model, the GAT–LGTA–LSTM model demonstrated an average increase in NSE of 0.07, an average increase in Kling–Gupta Efficiency (KGE) of 0.08, and an average reduction in mean absolute percent error (MAPE) of 0.12. The excellent performance of the proposed model is attributed to the following: (1) local attention mechanism assigns a higher weight to key global climate indices at a monthly scale, enhancing the ability of global and temporal attention mechanisms to capture the critical information at annual and interannual scales and (2) the global attention mechanism integrated with GAT effectively extracts crucial temporal and spatial information from precipitation and remotely-sensed elevation data. Furthermore, attention visualization reveals that various global climate indices contribute differently to runoff predictions across distinct months. The global climate indices corresponding to specific seasons or months should be selected to forecast the respective monthly runoff.

Background: tRNA-derived small RNAs (tsRNAs) are an emerging class of small noncoding RNAs derived from tRNA cleavage. Summary: With the development of high-throughput sequencing, various biological roles of tsRNAs have been gradually revealed, including regulation of mRNA stability, transcription, translation, direct interaction with proteins and as epigenetic factors, etc. Recent studies have shown that tsRNAs are also closely related to renal disease. In clinical acute kidney injury (AKI) patients and preclinical AKI models, the production and differential expression of tsRNAs in renal tissue and plasma were observed. Decreased expression of tsRNAs was also found in urine exosomes from chronic kidney disease patients. Dysregulation of tsRNAs also appears in models of nephrotic syndrome and patients with lupus nephritis. And specific tsRNAs were found in high glucose model in vitro and in serum of diabetic nephropathy patients. In addition, tsRNAs were also differentially expressed in patients with kidney cancer and transplantation. Key Messages: In the present review, we have summarized up-to-date works and reviewed the relationship and possible mechanisms between tsRNAs and kidney diseases.

Abstract Yellow-seed trait is a desirable breeding characteristic of rapeseed (Brassica napus) that could greatly improve seed oil yield and quality. However, the underlying mechanisms controlling this phenotype in B. napus plants are difficult to discern because of their complexity. Here, we assemble high-quality genomes of yellow-seeded (GH06) and black-seeded (ZY821). Combining in-depth fine mapping of a quantitative trait locus (QTL) for seed color with other omics data reveal BnA09MYB47a, encoding an R2R3-MYB-type transcription factor, as the causal gene of a major QTL controlling the yellow-seed trait. Functional studies show that sequence variation of BnA09MYB47a underlies the functional divergence between the yellow- and black-seeded B. napus. The black-seed allele BnA09MYB47aZY821, but not the yellow-seed allele BnA09MYB47aGH06, promotes flavonoid biosynthesis by directly activating the expression of BnTT18. Our discovery suggests a possible approach to breeding B. napus for improved commercial value and facilitates flavonoid biosynthesis studies in Brassica crops.

Abstract Purpose The association of NUCB-2/Nesfatin-1 with nasopharyngeal carcinoma (NPC) remains unclear. We clarified the role of NUCB-2/Nesfatin-1 in the development, progression and diagnosis of NPC. Materials and methods In nasopharyngeal carcinoma cell lines (5-8 F, 6-10B, CNE1, CNE2 and NP69), western blotting, MTT, EdU and other techniques were performed to investigate the role of NUCB-2 in nasopharyngeal carcinoma. 70 tissue samples (39 NPC and 31 rhinitis) and 140 serum samples (including NPC, rhinitis, other head and neck tumors and healthy control) were included to explore the expression of NUCB-2 and its metabolite Nesfatin-1 in tissues or serum of patients with nasopharyngeal carcinoma. Results NUCB-2 level in NPC tissue was higher than that in rhinitis tissue (P

Abstract Mitochondrial genomes (mitogenomes) of flowering plants vary greatly in structure and size, which can lead to frequent gene mutation, rearrangement, or recombination, then result in the cytoplasmic male sterile (CMS) mutants. In tobacco (Nicotiana tabacum), suaCMS lines are widely used in heterosis breeding; however, the related genetic regulations are not very clear. In this study, the cytological observation indicated that the pollen abortion of tobacco suaCMS(HD) occurred at the very early stage of the stamen primordia differentiation. In this study, the complete mitochondrial genomes of suaCMS(HD) and its maintainer HD were sequenced using the PacBio and Illumina Hiseq technology. The total length of the assembled mitogenomes of suaCMS(HD) and HD was 494,317 bp and 430,694 bp, respectively. Comparative analysis indicated that the expanded 64 K bases in suaCMS(HD) were mainly located in noncoding regions, and 23 and 21 big syntenic blocks (>5000 bp) were found in suaCMS(HD) and HD with a series of repeats. Electron transport chain‐related genes were highly conserved in two mitogenomes, except five genes (ATP4, ATP6, COX2, CcmFC, and SDH3) with substantial substitutions. Three suaCMS(HD)‐specific genes, orf261, orf291, and orf433, were screened. Sequence analysis and RT‐PCR verification showed that they were unique to suaCMS(HD). Further gene location analysis and protein property prediction indicated that all the three genes were likely candidates for suaCMS(HD). This study provides new insight into understanding the suaCMS mechanism and is useful for improving tobacco breeding.

Hepatopulmonary syndrome (HPS) is a severe lung injury caused by chronic liver disease, with limited understanding of the disease pathology. Exosomes are important mediators of intercellular communication that modulates various cellular functions by transferring a variety of intracellular components to target cells. Our recent studies have indicated that a new long noncoding RNA (lncRNA), PICALM-AU1, is mainly expressed in cholangiocytes, and is dramatically induced in the liver during HPS. However, the mechanism by which cholangiocyte-derived PICALM-AU1 regulates Endothelial-mesenchymal transition (EndMT) in HPS remains unclear. Here, we observed that PICALM-AU1 was synthesized in the cholangiocytes of the liver and then, secreted as exosomes into the serum; serum exosomal PICALM-AU1 levels were positively correlated with the severity of HPS in a rat model and in human patients. PICALM-AU1 carrying serum exosomes induced the EndMT of pulmonary microvascular endothelial cells (PMVECs) and promoted lung injury in vivo and in vitro. Furthermore, PICALM-AU1 acted as a molecular sponge for microRNA 144-3p (miR144-3p), resulting in the up-regulation of Zinc Finger E-Box Binding Homeobox 1 (ZEB1), a known target of EndMT and enhancement of EndMT, proliferation and migration of PMVECs. Taken together, our findings indicate that the cholangiocyte-derived exosomal lncRNA PICALM-AU1 plays a critical role in the EndMT in HPS lungs. Thus, it represents a potential therapeutic target for the treatment of HPS.

Background Congenital heart disease (CHDs) is the major cause of mortality from birth defects, affecting up to 1% of live births worldwide. However, the relationship between aluminum (Al) and iron (Fe) levels and the risk of CHDs has yielded inconsistent results. Methods We conducted a pair-matched case–control study that included 97 CHDs and 194 non-CHDs to investigate the association and interaction between Al/Fe exposure and the risk of CHDs in a birth cohort study in Lanzhou, China. Results Higher concentrations of cord blood Al were associated with a greater risk of total CHDs (aOR = 2.826, 95% CI [1.009–7.266]) and isolated CHDs (aOR = 10.713, 95% CI [1.017–112.851]) compared to the lowest Al level. Both in maternal blood and cord blood, a significant dose-effect was observed between Al level and total CHDs (Ptrend < 0.05), but a similar pattern was not observed for Fe. High Al in addition to high Fe appeared to elicit a stronger association with CHDs than both lowest tertile of Al and Fe level in umbilical cord blood, particularly for multiple CHDs, septal defects and patent ductus arteriosus. Conclusions Our study suggests that exposure to Al during pregnancy (≥2,408 μg/L) is significantly associated with an increased risk of CHDs in offspring, especially septal defects, and that high levels of Al and Fe are strongly correlated with fetal heart development. Further research is needed to understand the underlying mechanisms.

Aims The objective of this study is to examine the impact of inhibiting Sphingosine 1-phosphate receptor 2 (S1PR2) on liver inflammation, fibrogenesis, and changes of gut microbiome in the context of cholestasis-induced conditions. Methods The cholestatic liver injury model was developed by common bile duct ligation (CBDL). Sprague-Dawley rats were randomly allocated to three groups, sham operation, CBDL group and JTE-013 treated CBDL group. Biochemical and histological assessments were conducted to investigate the influence of S1PR2 on the modulation of fibrogenic factors and inflammatory infiltration. We conducted an analysis of the fecal microbiome by using 16S rRNA sequencing. Serum bile acid composition was evaluated through the utilization of liquid chromatography-mass spectrometry techniques. Results In the BDL rat model, the study findings revealed a significant increase in serum levels of conjugated bile acids, accompanied by an overexpression of S1PR2. Treatment with the specific inhibitor of S1PR2, known as JTE-013, resulted in a range of specific effects on the BDL rats. These effects included the improvement of liver function, reduction of liver inflammation, inhibition of hepatocyte apoptosis, and suppression of NETosis. These effects are likely mediated through the TCA/S1PR2/NOX2/NLRP3 pathway. Furthermore, the administration of JTE-013 resulted in an augmentation of the diversity of the bacterial community’s diversity, facilitating the proliferation of advantageous species while concurrently inhibiting the prevalence of detrimental bacteria. Conclusions The results of our study suggest that the administration of JTE-013 may have a beneficial effect in alleviating cholestatic liver disease and restoring the balance of intestinal flora.

Air pollution is a serious global public health problem. Air pollutants, especially fine particulate matter (PM2.5), are associated with increased risks of various diseases. In recent years, studies have confirmed that PM2.5 is closely related to chronic kidney disease, secondary kidney disease, and end-stage renal disease. This review summarized the effects of PM2.5 and its components on kidney diseases, and the potential mechanism of kidney injury induced by PM2.5 exposure from the aspects of inflammatory injury and oxidative stress, renal hemodynamic changes, and DNA damage and methylation, aiming to provide an insight for further mechanism research and the prevention and control of air pollution-induced kidney damage.

Abstract Activating transcription factor 4 (ATF4) is one of the key effectors of endoplasmic reticulum stress (ERS), ATF4/CHOP pathway-mediated ERS plays an important role in the progression of acute kidney disease (AKI). We have previously reported that Vitamin D receptor (VDR) exert renoprotection in rodent AKI models. However, whether ATF4, as well as ERS, is involved in the protective effect of VDR in ischemia-reperfusion (I/R) induced AKI is unknown. Herein, we showed that VDR agonist paricalcitol and VDR overexpression alleviated I/R-induced renal injury and cells apoptosis with decreased ATF4 and attenuated ERS, while VDR deletion significantly resulted in further increased ATF4, more drastic ERS and renal injury in I/R mice models. In addition, paricalcitol remarkably reduced Tunicamycin (TM) induced ATF4 and ERS with attenuated renal injury, while VDR deletion aggravated the above changes in TM mice models. Moreover, overexpression of ATF4 partially abolished the effect of paricalcitol against TM-induced ERS and apoptosis, while inhibition of ATF4 enhanced the protective effect of paricalcitol. Bioinformatics analysis indicated potential VDR binding sites on ATF4 promotor sequence which were further confirmed by ChIP-qPCR and dual-luciferase reporter gene assay. In conclusion, VDR attenuated I/R-induced AKI by suppressing ERS partly via transcriptional regulation of ATF4.

ObjectivesIt is easy to produce buckling distortion when welding thin plate butt joints, which affects the construction period, cost and performance, but this can be controlled by applying external restraints. MethodsFirst, a butt welding test of a thin plate under external restraints is carried out, and the out-of-plane deformation is measured by the optical surface scanning method. At the same time, finite element (FE) models in a free state and external restraint state are established, and the thermal mechanical phenomena of the two models are subjected to thermal-elastic-plastic FE analysis (TEP FE). The influence of different external restraint distributions on the welding buckling distortion of the joints is then studied, and reasons for controlling welding buckling distortion are analyzed from the perspective of longitudinal plastic strain and longitudinal contraction force.ResultsThe out-of-plane deformation of the corresponding model is in good agreement with the measured results, and milder than the out-of-plane deformation of the model in a free state. When external restraints are applied, the longitudinal plastic strain of the weld and its adjacent metal decreases, and the longitudinal contraction force of the thin plate also decreases.ConclusionsThe results verify that external restraints can effectively control welding buckling distortion, and the control effects are different depending on the external restraint distribution.

Background The role of inflammation in the pathogenesis of type 2 diabetes mellitus (T2DM) is well established. Lyn, a member of the nonreceptor protein tyrosine kinase Src family, has been reported to modulate inflammatory signaling pathways.Methods Lyn expression was assessed in kidney biopsies of 11 patients with diabetic kidney disease (DKD) and in kidney tissues of streptozotocin (STZ)-induced DKD mice. 102 recruited T2DM patients were divided into three groups: normoalbuminuria, microalbuminuria and macroalbuminuria. Twenty-one healthy volunteers were recruited as a control group. Clinical data, blood and urine samples of all individuals were collected for analysis.Results Lyn expression was augmented in the kidneys of DKD patients and STZ-induced diabetic mice. Compared with control and normoalbuminuria groups, both mRNA and protein expression of Lyn in peripheral blood mononuclear cells (PBMCs) in the macroalbuminuria group were significantly increased (p

AbstractPurpose The purpose of this study was to investigate the association between serum proprotein convertase subtilisin/kexin type 9 (PCSK9) levels and renal function impairment in type 2 diabetes mellitus (T2DM) patients.Methods PCSK9 levels were measured in T2DM patients, streptozotocin plus high-fat diet (STZ + HFD) mice, human proximal tubular epithelial (HK-2) cells treated with high glucose plus palmitic acid (HGPA) and the corresponding control groups. The T2DM patients were further divided into three groups according to serum PCSK9 levels. An analysis of clinical data was conducted, and a binary logistic regression model was used to test the relationship between potential predictors and urine albumin/urine creatinine ratio (UACR) and estimated glomerular filtration rate (eGFR).Results PCSK9 levels were higher in the DM group than in the control group in humans, mice and HK-2 cells. The systolic blood pressure (SBP), serum creatinine (Scr), blood urea nitrogen (BUN), triglyceride (TG), and urine α1-MG/urine creatinine ratio (UαCR) values in PCSK9 tertile 3 were significantly higher than those in PCSK9 tertile 1 (p

S14G-humanin (HNG), an analog of the mitochondria-derived peptide humanin, has demonstrated protective effects against various cardiovascular diseases. However, the specific pharmacological effects of HNG in heart failure (HF) have not been previously reported. Therefore, in this study, we aimed to investigate the potential protective effect of HNG in HF using a mouse model. HF was induced in mice through intraperitoneal injection of isoproterenol or transverse aortic constriction, followed by separate administration of HNG to assess its therapeutic impact. Our results revealed that HNG treatment significantly delayed the onset of cardiac dysfunction and structural remodeling in the HF mouse model. Furthermore, HNG administration was associated with reduced infiltration of inflammatory cells, improved myocardial fibrosis, and attenuation of cardiomyocyte apoptosis in the treated cardiac tissues. Additionally, we identified the involvement of the transforming growth factor-beta signaling pathway in the beneficial effects of HNG in isoproterenol-induced HF mice. Collectively, these findings underscore the therapeutic potential of HNG in preventing the progression of HF, as demonstrated in two distinct HF mouse models.

Fine particulate matter (PM2.5)-related health issues have received increasing attention as a worldwide public health problem, and PM2.5-related chronic kidney disease (CKD) has been emerging over the years. Limited research has focused on the mechanism of PM2.5-induced kidney disease. To investigate the impact of PM2.5 on the kidney and its potential mechanism, we generated a PM2.5-exposed C57BL/6 mouse model by using Shanghai Meteorological and Environment Animal Exposure System (Shanghai-METAS) for 12 weeks, urine, blood and kidney tissues were collected. The pathological changes and the function of the kidney were measured after PM2.5 exposure for 12 weeks. Along with glomerular damage, tubular damage was also severe in PM2.5-induced mice. The results of mRNA-seq indicate that pyroptosis is involved. Pyroptosis is defined as caspase-1-dependent programmed cell death in response to insults. The expression of the nucleotide-binding and oligomerization domain-like receptor family pyrin domain containing 3 (NLRP3), Caspase-1, gasdermin D (GSDMD) and IL-1β was detected. NLRP3 inflammasome activation and subsequent pyroptosis were observed in PM2.5-exposed kidney tissues and PM2.5-exposed Bumpt cells too. At the meantime, the inhibitors of NLRP3 and caspase-1 were applied to the PM2.5 exposed Bumpt cells. It turned out to have a significant rescue effect of the inhibitors. This study revealed new insights into PM2.5-induced kidney injury and specific kidney pathological damage, as well as morphological changes, and defined the important role of pyroptosis in PM2.5-induced kidney dysfunction.

Abstract Cuproptosis is a newly form of cell death. Cuproptosis related lncRNA in lung adenocarcinoma (LUAD) has also not been fully elucidated. In the present study, we aimed to construct a prognostic signature based on cuproptosis-related lncRNA in LUAD and investigate its association with immunotherapy response. The RNA-sequencing data, clinical information and simple nucleotide variation of LUAD patients were obtained from TCGA database. The LASSO Cox regression was used to construct a prognostic signature. The CIBERSORT, ESTIMATE and ssGSEA algorithms were applied to assess the association between risk score and TME. TIDE score was applied to reflect the efficiency of immunotherapy response. The influence of overexpression of lncRNA TMPO-AS1 on A549 cell was also assessed by in vitro experiments. The lncRNA prognostic signature included AL606834.1, AL138778.1, AP000302.1, AC007384.1, AL161431.1, TMPO-AS1 and KIAA1671-AS1. Low-risk group exhibited much higher immune score, stromal score and ESTIMATE score, but lower tumor purity compared with high-risk groups. Also, low-risk group was associated with a much higher score of immune cells and immune related function sets, indicating an immune activation state. Low-risk patients had relative higher TIDE score and lower TMB. External validation using IMvigor210 immunotherapy cohort demonstrated that low-risk group had a better prognosis and might more easily benefit from immunotherapy. Overexpression of lncRNA TMPO-AS1 promoted the proliferation, migration and invasion of A549 cell line. The novel cuproptosis-related lncRNA signature could predict the prognosis of LUAD patients, and helped clinicians stratify patients appropriate for immunotherapy and determine individual therapeutic strategies.

Abstract Psoriatic arthritis (PsA) is associated with psoriasis, featured by its irreversible joint symptoms. Despite the significant impact on the healthcare system, it is still challenging to leverage machine learning or statistical models to predict PsA and its progression, or analyze drug efficacy. With 3961 patients’ clinical records, we developed a machine learning model for PsA diagnosis and analysis of PsA progression risk, respectively. Furthermore, general additive models (GAMs) and the Kaplan–Meier (KM) method were applied to analyze the efficacy of various drugs on psoriasis treatment and inhibiting PsA progression. The independent experiment on the PsA prediction model demonstrates outstanding prediction performance with an AUC score of 0.87 and an AUPR score of 0.89, and the Jackknife validation test on the PsA progression prediction model also suggests the superior performance with an AUC score of 0.80 and an AUPR score of 0.83, respectively. We also identified that interleukin-17 inhibitors were the more effective drug for severe psoriasis compared to other drugs, and methotrexate had a lower effect in inhibiting PsA progression. The results demonstrate that machine learning and statistical approaches enable accurate early prediction of PsA and its progression, and analysis of drug efficacy.

Abstract Objective To assess the repair method of exposure or fracture of the porous high-density polyethylene ear framework after total auricle reconstruction. Study design A prospective case study. Methods From April 2018 to October 2021, 11 patients with framework exposure or fracture after total auricle reconstruction were admitted to the hospital for repair. In these 11 patients, the repair was performed using (1) a temporal muscle flap combined with free skin graft in 5 patients, (2) a mastoid fascia flap combined with free skin graft in 2 patients, (3) a simple local skin flap in 1 patient, (4) combination of a temporalis muscle flap and a mastoid fascia flap together with free skin graft in 2 patients, and (5) a Su-Por helix material combined with a temporal muscle flap and free skin graft in 1 patient. Results After follow-up for 3–36 months, except for one patient in whom local exposure again occurred at the same site, the framework was in a good shape in the other patients, and all the skin graft survived. Conclusion The defect of the upper part of the auricle can be repaired using a temporal muscle flap combined with temporal muscle fascia and skin graft. The defect of the middle and lower part of the auricle can be repaired using a mastoid fascia flap combined with skin graft. For framework fracture, the damaged site can be first strengthened with another ear material and then combined with the adjacent fascia flap and free skin graft.

Aims The role of probiotics in the management of diabetic kidney disease (DKD) has been shown. Several current trials are investigating the effect of probiotics, which are widely used to modulate biomarkers of renal function, glucose, lipids, inflammation and oxidative stress in patients with DKD. However, their findings are controversial. This study aimed to systematically evaluate the impact of probiotics on patients with DKD via meta-analysis.Methods PubMed, The Cochrane Library, Web of Science, Scopus, Embase, China National Knowledge Infrastructure, Chinese Wanfang Database and Chinese VIP Database were searched for relevant studies from the establishment of these databases to September 2021. The pooled results evaluated the impact of probiotics on renal function, glucose, lipids, inflammation and oxidative stress indicators in patients with DKD. Additionally, subgroup analysis was performed based on intervention duration, probiotic dose and probiotic consumption patterns, respectively.Results Ten trials that included 552 participants were identified for analysis. Compared with the controls, probiotics significantly decreased serum creatinine (Scr) [WMD = −0.17 mg/dL; 95%CI = −0.29, −0.05; p = 0.004], blood urea nitrogen (BUN) [WMD = −1.36 mg/dL; 95%CI = −2.20, −0.52; p = 0.001], cystatin C (Cys C) [WMD = −29.50 ng/mL; 95%CI = −32.82, −26.18; p

Previous studies suggested a chemokine receptor governed gradient of Rac1 activity is essential for collective guidance of Drosophila border cells. Here, Zhou et al. report that two distinct Rac1 pools at protrusions and cables, not Rac1 activity gradient, integrate the direction and coordination for collective guidance.

ObjectiveNon-invasive methods for hemoglobin (Hb) monitoring can provide additional and relatively precise information between invasive measurements of Hb to help doctors' decision-making. We aimed to develop a new method for Hb monitoring based on mask R-CNN and MobileNetV3 with eye images as input.MethodsSurgical patients from our center were enrolled. After image acquisition and pre-processing, the eye images, the manually selected palpebral conjunctiva, and features extracted, respectively, from the two kinds of images were used as inputs. A combination of feature engineering and regression, solely MobileNetV3, and a combination of mask R-CNN and MobileNetV3 were applied for model development. The model's performance was evaluated using metrics such as R2, explained variance score (EVS), and mean absolute error (MAE).ResultsA total of 1,065 original images were analyzed. The model's performance based on the combination of mask R-CNN and MobileNetV3 using the eye images achieved an R2, EVS, and MAE of 0.503 (95% CI, 0.499–0.507), 0.518 (95% CI, 0.515–0.522) and 1.6 g/dL (95% CI, 1.6–1.6 g/dL), which was similar to that based on MobileNetV3 using the manually selected palpebral conjunctiva images (R2: 0.509, EVS:0.516, MAE:1.6 g/dL).ConclusionWe developed a new and automatic method for Hb monitoring to help medical staffs' decision-making with high efficiency, especially in cases of disaster rescue, casualty transport, and so on.

The milestone discovery of GW170817-GRB 170817A-AT 2017gfo has shown that gravitational waves (GWs) could be produced during the merger of a neutron star–neutron star/black hole and that in electromagnetic (EM) waves, a gamma-ray burst (GRB) and a kilonova (KN) are generated in sequence after the merger. Observationally, however, EM properties before the merger phase are still unclear. Here we report a peculiar precursor in a KN-associated long-duration GRB 211211A, providing evidence of the EM before the merger. This precursor lasts ∼0.2 s, and the waiting time between the precursor and the main burst is ∼1 s, comparable to that between GW170817 and GRB 170817A. The spectrum of the precursor could be well fit with a nonthermal cutoff power-law model instead of a blackbody. In particular, a ∼22 Hz quasiperiodic oscillation candidate (∼3 σ ) is detected in the precursor. These temporal and spectral properties indicate that this precursor is probably produced by a catastrophic flare accompanied with magnetoelastic or crustal oscillations of a magnetar in a binary compact merger. The strong magnetic field of the magnetar can also account for the prolonged duration of GRB 211211A. However, it poses a challenge to reconcile the rather short lifetime of a magnetar with the rather long spiraling time of a binary neutron star system only by the GW radiation before the merger.

Systematic domestic water demand prediction is of great importance for social and economic sustainable development. To explain the system of domestic water demand prediction more completely, a system dynamic model based on the social-hydrology method was proposed in this paper. The key natural and socio-economic factors that affect the domestic water demand most were identified and investigated. The prediction equations of water price considering the feedback between humans and nature were deduced. The expressions of water-saving consciousness were proposed for the first time. Furthermore, the differential and difference equations for domestic water demand prediction were established to realize the future domestic water demand forecasts considering the natural and social driving forces. Finally, three scenarios were designed to investigate the impact of climate change and economic development on the domestic water demand. The upper and middle Pearl River Basin was selected as a case study. The predicted domestic water demand is consistent with the historical results, which demonstrates that the proposed model can be well used for the prediction of the domestic water demand. Under the three scenarios, the domestic water demand increased by 33, 27 and 18% in 2050 compared with that in 2017, respectively. HIGHLIGHTS This study combined a system dynamic model with social-hydrology methods.; The mechanism of water price formation considering the feedback between humans and water resources was deduced.; The expressions of water-saving consciousness were proposed for the first time.; Three scenarios were designed to investigate the impact of climate change and economic development on the domestic water demand.;

Abstract Background Heterosis is an important biological phenomenon in which the hybrids exceed the parents in many traits. However, the molecular mechanism underlying seedling heterosis remains unclear. Results In the present study, we analyzed the leaf transcriptomes of strong hybrids (AM, HM) and weak hybrids (CM, HW) and their parents (A, C, H, M, and W) at two periods. Phenotypically, hybrids had obvious biomass heterosis at the seedling stage, with statistically significant differences between the strong and weak hybrids. The transcriptomic analysis demonstrated that the number of differentially expressed genes (DEGs) between parents was the highest. Further analysis showed that most DEGs were biased toward parental expression. The biological processes of the two periods were significantly enriched in the plant hormone signal transduction and photosynthetic pathways. In the plant hormone signaling pathway, DEG expression was high in hybrids, with expression differences between strong and weak hybrids. In addition, DEGs related to cell size were identified. Similar changes were observed during photosynthesis. The enhanced leaf area of hybrids generated an increase in photosynthetic products, which was consistent with the phenotype of the biomass. Weighted gene co-expression network analysis of different hybrids and parents revealed that hub genes in vigorous hybrid were mainly enriched in the plant hormone signal transduction and regulation of plant hormones. Conclusion Plant hormone signaling and photosynthesis pathways, as well as differential expression of plant cell size-related genes, jointly regulate the dynamic changes between strong and weak hybrids and the generation of seedling-stage heterosis. This study may elucidate the molecular mechanism underlying early biomass heterosis and help enhance canola yield.

Chloroplasts are essential for plant growth and development, as they play a key role in photosynthesis. The chloroplast biogenesis process is complex and its regulatory mechanism remains elusive. We characterized a spontaneous Brassica napus (rapeseed) mutant, ytg, that showed a delayed greening phenotype in all green organs and retarded growth. We identified BnaA02.YTG1 encoding a chloroplast-localized tetratricopeptide repeat protein widely expressed in rapeseed tissues. We speculated that the ytg phenotype was caused by the deletion of BnaA02.YTG1 based on sequence comparison of 4608 (with normal green leaves, isolated from the elite Chinese rapeseed cultivar ZS11) and ytg combined with transcriptome data and CRISPR/Cas9 gene editing results. The homologous gene (BnaC02.YTG1) restored the phenotype of the mutant. BnaA02.YTG1 interacted with MORF2, MORF8, and OZ1. RNA editing of the ndhD-2, ndhF-290, petL-5, and ndhG-50 plastid transcripts was affected in ytg. These findings suggested that BnaA02.YTG1 participates in RNA editing events. We predicted 29 RNA editing sites in the chloroplast of Brassica napus by comparison with the Arabidopsis chloroplast genome. We conclude that BnaA02.YTG1 affects the posttranscriptional regulation of plastid gene expression and suggest that a tetratricopeptide repeat protein is involved in the chloroplast RNA editing in rapeseed.

Abstract Background It has been established that lung cancer is the leading cause of all cancer deaths. This study sought to analyze the epidemiological trends of lung cancer over the past 30 years worldwide. Methods Estimates, including the global, regional, national prevalence, incidence, and years lived with disability (YLDs) of lung cancer from 1990 to 2019, were extracted from the Global Burden of Disease Study 2019 to assess the spatiotemporal dynamics in cases and age-standardized rates (ASR). The estimated annual percentage change (EAPC) was calculated to evaluate the variation in ASR. Besides, estimates of age-sex specific prevalence, decomposition analysis for incident cases, and correlation analysis of the EAPC were conducted in our study. Results Globally, the ASR of lung cancer prevalence, incidence and YLDs in 2019 were 38.84/100,000 persons, 27.66/100,000 persons, and 6.62/100,000 persons, respectively. Over the past 30 years, the ASR of incidence (EAPC = -0.09) decreased, although that of prevalence (EAPC = 0.51) and YLDs (EAPC = 0.03) increased. The global prevalence counts was greater in males than females at all age groups and increased with age, peaking in the 65–69 age group for both sexes. The increase in incidence was mainly attributed to population aging. For YLDs, EAPC was negatively correlated with the human development index (p = 0.0008) and ASR (p

Abstract Background Dynamic prediction of patient mortality risk in the ICU with time series data is limited due to high dimensionality, uncertainty in sampling intervals, and other issues. A new deep learning method, temporal convolution network (TCN), makes it possible to deal with complex clinical time series data in ICU. We aimed to develop and validate it to predict mortality risk using time series data from MIMIC III dataset. Methods A total of 21,139 records of ICU stays were analysed and 17 physiological variables from the MIMIC III dataset were used to predict mortality risk. Then we compared the model performance of the attention-based TCN with that of traditional artificial intelligence (AI) methods. Results The area under receiver operating characteristic (AUCROC) and area under precision-recall curve (AUC-PR) of attention-based TCN for predicting the mortality risk 48 h after ICU admission were 0.837 (0.824 -0.850) and 0.454, respectively. The sensitivity and specificity of attention-based TCN were 67.1% and 82.6%, respectively, compared to the traditional AI method, which had a low sensitivity (

Background: In addition to intrahepatic angiogenesis, patients with cholestasis cirrhosis develop extrahepatic vasculature disorders and functional disturbances of multiple organ systems. Without effective intervention, these vascular disorders will eventually turn into multiple organs vascular syndromes, including the brain, lung and other organ systems. However, studies on the pathogenesis of vascular alterations among extrahepatic organ disturbances are still carried out separately, which hampered the successful translation of preclinical studies to the human setting and required further mechanistic insight into these complications. This study aims to investigate the relationship between extrahepatic angiogenesis and multiple organ impairment, and whether the vascular endothelial growth factor (VEGF) family members and their receptors are involved in this process. Methods: Pathological changes of the multiple organs were determined by histopathological and immunohistochemical staining in the established common bile duct ligation (CBDL) rats, and angiogenesis was estimated by microvessel density (MVD). Levels of the VEGF family members and their receptors in the serum and organ tissues were also measured by using enzyme-linked immunosorbent assays. Results: The MVD and VEGF family members and their receptors were significantly increased in CBDL rats with multiple organ injury, especially in the liver, lung and cerebral cortex. Meanwhile, we noticed moderate elevation of soluble receptor of the vascular endothelial growth factor-1 (sFlt-1) in the liver, lung, and cerebral cortex, whereas the levels of placental growth factor (PLGF) increased significantly. Conclusions: Extrahepatic angiogenesis may represent a common pathophysiological basis for multiple organ dysfunction and the sFlt-1/PLGF ratio could offer an avenue for further studies to target extrahepatic angiogenesis in cholestatic cirrhosis.

Objective: The aim of this study was to explore the clinical value of lymph node dissection (LND) for intrahepatic cholangiocarcinoma (ICC). Methods: Clinical and pathological data were collected from 147 ICC patients who attended two tertiary centers over the past 5 years. The patients were classified into two groups: the LND group (group A) and the no-performance LND (NLND) group (group B). Clinical and pathological parameters were compared between the two groups to analyze the impact of LND on the long-term survival time of ICC patients. Results: Of the 147 patients, 54.4% (80) received LND and 42.5% (34/80) of these were found to have lymph node metastasis (LNM). LND did not increase postoperative complications (27.5%, P = 0.354), but postoperative hospital stays were longer (12.2 ± 6.3 d, P = 0.005) in group A compared with group B (20.9%, 9.5 ± 3.5 d). The 5-year survival rates of groups A and B are almost similar (21% vs 29%, P = 0.905). The overall survival rate of cN0 (diagnosis obtained by imaging) is better than pN1 (diagnosis obtained by histopathology), but lower than pN0 (all P

Introduction C-peptide has been reported to provide renoprotective effects. This study aims to explore the relationship between C-peptide and progression of renal function in patients with type 2 diabetes mellitus (T2DM).Research design and methods We retrospectively collected clinical data from 854 T2DM patients over a median follow-up of 5 years. Renal events included an annual decline in estimated glomerular filtration rate (eGFR), a rapid kidney function decline and a renal composite endpoint. A linear mixed-effects model and Cox regression analysis were used to investigate the effect of C-peptide on renal events, and a subgroup analysis was performed after stratification by risk factors.Results The highest-level C-peptide group had a smaller annual eGFR decline compared with those in the group with the lowest level (p

ObjectivesThis study aimed to evaluate the safety and feasibility of robotic-assisted thoracic surgery (RATS) after neoadjuvant chemoimmunotherapy in NSCLC.MethodsWe retrospectively collected data for NSCLC patients who received thoracic surgery after neoadjuvant chemoimmunotherapy from May 2020 to August 2022. Surgery details, pathological response, and perioperative outcome were compared between video-assisted thoracic surgery (VATS) group and RATS group. Inverse probability of treatment weighting (IPTW) was used to equal the baseline characteristics.ResultsA total of 220 patients were divided into 78 VATS patients and 142 RATS patients. There was no 90-day mortality in either group. RATS patients demonstrated better results in conversion rate to thoracotomy (VATS vs. RATS: 28.2% vs. 7.5%, P < 0.001), number of lymph node stations harvested (5.63 ± 1.75 vs. 8.09 ± 5.73, P < 0.001), number of lymph nodes harvested (13.49 ± 9.325 vs. 20.35 ± 10.322, P < 0.001), yield pathologic-N (yp-N) assessment (yp-N0, 88.5% vs. 67.6%; yp-N1, 7.6% vs. 12.6%; yp-N2, 3.8% vs. 19.7%; P < 0.001), and visual analog scale pain score after surgery (4.41 ± 0.93 vs. 3.77 ± 1.21, P=0.002). However, there were no significant differences in pathological response evaluation for neoadjuvant chemoimmunotherapy (P = 0.493) and complication rate (P = 0.803). After IPTW-adjustment, these results remained constant.ConclusionsRATS reduced the risk of conversion to thoracotomy, provided a better yp-N stage evaluation, and improved pain score; this suggests that RATS is safe and feasible for NSCLC patients after neoadjuvant chemoimmunotherapy.

Background: Our previous study showed that vitamin D (VD)-vitamin D receptor (VDR) plays a nephroprotective role in lipopolysaccharide (LPS)-induced acute kidney injury (AKI). Recently, glucose metabolism reprogramming was reported to be involved in the pathogenesis of AKI.Objective: To investigate the role of VD-VDR in glucose metabolism reprogramming in LPS-induced AKI.Methods: We established a model of LPS-induced AKI in VDR knockout (VDR-KO) mice, renal proximal tubular-specific VDR-overexpressing (VDR-OE) mice and wild-type C57BL/6 mice. In vitro, human proximal tubular epithelial cells (HK-2 cells), VDR knockout and VDR overexpression HK-2 cell lines were used.Results: Paricalcitol (an active vitamin D analog) or VDR-OE reduced lactate concentration, hexokinase activity and PDHA1 phosphorylation (a key step in inhibiting aerobic oxidation) and simultaneously ameliorated renal inflammation, apoptosis and kidney injury in LPS-induced AKI mice, which were more severe in VDR-KO mice. In in vitro experiments, glucose metabolism reprogramming, inflammation and apoptosis induced by LPS were alleviated by treatment with paricalcitol or dichloroacetate (DCA, an inhibitor of p-PDHA1). Moreover, paricalcitol activated the phosphorylation of AMP-activated protein kinase (AMPK), and an AMPK inhibitor partially abolished the protective effect of paricalcitol in LPS-treated HK-2 cells.Conclusion: VD-VDR alleviated LPS-induced metabolic reprogramming in the kidneys of AKI mice, which may be attributed to the inactivation of PDHA1 phosphorylation via the AMPK pathway.

In order to study the volatile and semivolatile components changes of cut tobacco in the drying process, the cut tobacco were determined by headspace-gas chromatography/mass spectrometry (HS-GC/MS). Principal component analysis (PCA) and similarity analysis were used to analyze the HS-GC/MS results. Based on the similarity, the drying conditions and drying mechanism have been studied. The results showed that the increase in water content would reduce the dying rate, and if the temperature increased, the dying rate increased. The preliminary study on the drying kinetics of the drying process shows that Henderson and Pabis model appeared to be the most suitable for describing the drying process of cut tobacco, and the drying activation energy is 111.9 kJ.

Although utilization of heterosis has largely improved the yield of many crops worldwide, the underlying molecular mechanism of heterosis, particularly for allopolyploids, remains unclear. Here, we compared epigenome and transcriptome data of an elite hybrid and its parental lines in three assessed tissues (seedling, flower bud, and silique) to explore their contribution to heterosis in allopolyploid B. napus. Transcriptome analysis illustrated that a small proportion of non-additive genes in the hybrid compared with its parents, as well as parental expression level dominance, might have a significant effect on heterosis. We identified histone modification (H3K4me3 and H3K27me3) variation between the parents and hybrid, most of which resulted from the differences between parents. H3K4me3 variations were positively correlated with gene expression differences among the hybrid and its parents. Furthermore, H3K4me3 and H3K27me3 were rather stable in hybridization and were mainly inherited additively in the B. napus hybrid. Together, our data revealed that transcriptome reprogramming and histone modification remodeling in the hybrid could serve as valuable resources for better understanding heterosis in allopolyploid crops.