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Abstract Background Dyslipidemia frequently coexists with hypertension in the population. Apolipoprotein B (ApoB) is increasingly considered a more potent predictor of cardiovascular disease (CVD). Abnormal levels of serum ApoB can potentially impact the mortality risk. Methods The prospective cohort study employed data from the National Health and Nutrition Examination Survey (NHANES), which was performed between 2005 and 2016, with follow-ups extended until December 2019. Serum ApoB concentrations were quantified using nephelometry. In line with the NHANES descriptions and recommendations, the reference ranges for ApoB concentrations are 55–140 and 55–125 mg/dL for men and women, respectively. Participants were categorized into low, normal, and high ApoB levels. The low and high groups were combined into the abnormal group. In this study, all-cause mortality (ACM) and CVD mortality (CVM) were the endpoints. Survey-weighted cox hazards models were used for evaluating the correlation between serum ApoB levels and ACM and CVM. A generalized additive model (GAM) was employed to examine the dose-dependent relationship between ApoB levels and mortality risk. Results After a median of 95 (interquartile range: 62–135) months of follow-up, 986 all-cause and 286 CVD deaths were recorded. The abnormal ApoB group exhibited a trend toward an elevated risk of ACM in relative to the normal group (HR 1.22, 95% CI: 0.96–1.53). The risk of CVM was elevated by 76% in the ApoB abnormal group (HR 1.76, 95% CI: 1.28–2.42). According to the GAM, there existed a nonlinear association between serum ApoB levels and ACM (P = 0.005) and CVM (P = 0.009). Conclusions In the US hypertensive population, serum Apo B levels were U-shaped and correlated with ACM and CVM risk, with the lowest risk at 100 mg/dL. Importantly, abnormal Apo B levels were related to an elevated risk of ACM and CVM. These risks were especially high at lower Apo B levels. The obtained findings emphasize the importance of maintaining appropriate Apo B levels to prevent adverse outcomes in hypertensive individuals.

Abstract Cholesterol 25‐hydroxylase (CH25H), an enzyme involved in cholesterol metabolism, regulates inflammatory responses and lipid metabolism. However, its role in kidney disease is not known. The author found that CH25H transcript is expressed mostly in glomerular and peritubular endothelial cells and that its expression increased in human and mouse diabetic kidneys. Global deletion of Ch25h in Leprdb/db mice aggravated diabetic kidney disease (DKD), which is associated with increased endothelial cell apoptosis. Treatment of 25‐hydroxycholesterol (25‐HC), the product of CH25H, alleviated kidney injury in Leprdb/db mice. Mechanistically, 25‐HC binds to GTP‐binding protein ADP‐ribosylation factor 4 (ARF4), an essential protein required for maintaining protein transport in the Golgi apparatus. Interestingly, ARF4's GTPase‐activating protein ASAP1 is also predominantly expressed in endothelial cells and its expression increased in DKD. Suppression of ARF4 activity by deleting ARF4 or overexpressing ASAP1 results in endothelial cell death. These results indicate that 25‐HC binds ARF4 to inhibit its interaction with ASAP1, and thereby resulting in enhanced ARF4 activity to confer renoprotection. Therefore, treatment of 25‐HC improves kidney injury in DKD in part by restoring ARF4 activity to maintain endothelial cell survival. This study provides a novel mechanism and a potential new therapy for DKD.

Abstract Background Estimated pulse wave velocity (ePWV) has been proposed as a potential approach to estimate carotid-femoral pulse wave velocity. However, the potential of ePWV in predicting all-cause mortality (ACM) and cardiovascular disease mortality (CVM) in the general population is unclear. Methods We conducted a prospective cohort study using the data of 33,930 adults (age ≥ 20 years) from the National Health and Nutrition Examination Survey (NHANES) from 1999 to 2014 until the end of December 2019. The study outcomes included ACM and CVM. Survey-weighted Cox proportional hazards models were used to assess hazard ratios (HRs) and 95% confidence intervals (CIs) to determine the association between ePWV and ACM and CVM. To further investigate whether ePWV was superior to traditional risk factors in predicting ACM and CVM, comparisons between ePWV and the Framingham Risk Score (FRS) and Pooled Cohort Equations (PCE) models were performed. Integrated Discriminant Improvement (IDI) and Net Reclassification Improvement (NRI) were employed to analyze differences in predictive ability between models. Results The weighted mean age of the 33,930 adults included was 45.2 years, and 50.28% of all participants were men. In the fully adjusted Cox regression model, each 1 m/s increase in ePWV was associated with 50% and 49% increases in the risk of ACM (HR 1.50; 95% CI, 1.45–1.54) and CVM (HR 1.49; 95% CI, 1.41–1.57), respectively. After adjusting for FRS, each 1 m/s increase in ePWV was still associated with 29% (HR 1.29; 95% CI, 1.24–1.34) and 34% (HR 1.34; 95% CI, 1.23–1.45) increases in the risk of ACM and CVM, respectively. The area under the curve (AUC) predicted by ePWV for 10-year ACM and CVM were 0.822 and 0.835, respectively. Compared with the FRS model, the ePWV model improved the predictive value of ACM and CVM by 5.1% and 3.8%, respectively, with no further improvement in event classification. In comparison with the PCE model, the ePWV model’s ability to predict 10-year ACM and CVM was improved by 5.1% and 3.5%, and event classification improvement was improved by 34.5% and 37.4%. Conclusions In the U.S. adults, ePWV is an independent risk factor for ACM and CVM and is independent of traditional risk factors. In the general population aged 20 to 85 years, ePWV has a robust predictive value for the risk of ACM and CVM, superior to the FRS and PCE models. The predictive power of ePWV likely originates from the traditional risk factors incorporated into its calculation, rather than from an indirect association with measured pulse wave velocity.

Abstract Background and Aims Primary aldosteronism (PA) is an adrenal disorder of autonomous aldosterone secretion which promotes arterial injury. We aimed to explore whether PA is causally associated with lower-extremity arterial disease (LEAD). Methods We included 39,713 patients with diabetes and 419,312 participants without diabetes from UK Biobank. We derived a polygenic risk score (PRS) for PA based on previous genome-wide association studies (GWAS). Outcomes included LEAD and LEAD related gangrene or amputation. We conducted a two-sample Mendelian randomization analysis for PA and outcomes to explore their potential causal relationship. Results In whole population, individuals with a higher PA PRS had an increased risk of LEAD. Among patients with diabetes, compared to the subjects in the first tertile of PA PRS, subjects in the third tertile showed a 1.24-fold higher risk of LEAD (OR 1.24, 95% CI 1.03–1.49) and a 2.09-fold higher risk of gangrene (OR 2.09, 95% CI 1.27–3.44), and 1.72-fold higher risk of amputation (OR 1.72, 95% CI 1.10–2.67). Among subjects without diabetes, there was no significant association between PA PRS and LEAD, gangrene or amputation. Two-sample Mendelian randomization analysis indicated that genetically predictors of PA was significantly associated with higher risks of LEAD and gangrene (inverse variance weighted OR 1.20 [95% CI 1.08–1.34]) for LEAD, 1.48 [95% CI 1.28–1.70] for gangrene), with no evidence of significant heterogeneity or directional pleiotropy. Conclusions Primary aldosteronism is genetically and causally associated with higher risks of LEAD and gangrene, especially among patients with diabetes. Targeting on the autonomous aldosterone secretion may prevent LEAD progression.

Glypicans are closely associated with organ development and tumorigenesis in animals. Dally-like (Dlp), a membrane-bound glypican, plays pivotal roles in various biological processes in Drosophila. In this study, we observed that an excess of Dlp led to the malformation of legs, particularly affecting the distal part. Accordingly, the leg disc was shrunken and frequently exhibited aberrant morphology. In addition, elevated Dlp levels induced ectopic cell death with no apparent cell proliferation changes. Furthermore, Dlp overexpression in the posterior compartment significantly altered Wingless (Wg) distribution. We observed a marked expansion of Wg distribution within the posterior compartment, accompanied by a corresponding decrease in the anterior compartment. It appears that excess Dlp guides Wg to diffuse to cells with higher Dlp levels. In addition, the distal-less (dll) gene, which is crucial for leg patterning, was up-regulated significantly. Notably, dachshund (dac) and homothorax (hth) expression, also essential for leg patterning and development, only appeared to be negligibly affected. Based on these findings, we speculate that excess Dlp may contribute to malformations of the distal leg region of Drosophila, possibly through its influence on Wg distribution, dll expression and induced cell death. Our research advances the understanding of Dlp function in Drosophila leg development.

Bamboo is a natural vascular bundle (VB) reinforced composite material used in more than 10 fields such as construction and furniture. The nodes in bamboo are crucial to its mechanical properties, but understanding of its performance is limited by lack of knowledge about the three-dimensional (3D) structure of the node. This work aimed to non-destructively identify the multi-dimensional characteristics of the VB in a bamboo branched node (BN) using X-ray microtomography (µCT). The VB was segmented from the BN using deep learning combined with the Watershed algorithm. The 3D model reconstruction and characterization of the VB were also conducted. It was found that the structure of VBs showed significant changes along the height of the BN. The VBs formed a complex 3D structure, VBs of the culm are connected with those of the branch, and the connectivity of the conducting tissue and fibers was 88.91% and 99.95%, respectively. The conducting tissue and the fibers had similar shapes but varying thicknesses, which enabled VBs to perform both water transport and mechanical support functions. The volumes fraction of parenchyma, fibers, and conducting tissue in the BN were 61.3%, 35.3%, and 3.4%, respectively, but the tissue proportion of the different heights of the BN varied from each other. The nodal ridge was a mechanical weak point of the BN, with a maximum fibers proportion of 43.8%. This study contributes to understanding the relationship of VBs between the branch and the culm. It provides a structural perspective for understanding the mechanical properties of BN and a theoretical basis for optimizing bamboo utilization efficiency.

BackgroundSignificant evidence suggests that asthma might originate from low-grade systemic inflammation. Previous studies have established a positive association between the systemic immune-inflammation index (SII) and the systemic inflammation response index (SIRI) levels and the risk of stroke. However, it remains unclear whether SII, SIRI and the prevalence of stroke are related in individuals with asthma.MethodsThe present cross-sectional study used data from the National Health and Nutrition Examination Survey (NHANES) conducted between 1999 and 2018. SII was calculated using the following formula: (platelet count × neutrophil count)/lymphocyte count. SIRI was calculated using the following formula: (neutrophil count × monocyte count)/lymphocyte count. The Spearman rank correlation coefficient was used to determine any correlation between SII, SIRI, and the baseline characteristics. Survey-weighted logistic regression was employed to calculate odds ratios (ORs) and 95% confidence intervals (CIs) to determine the association between SII, SIRI, and stroke prevalence. The predictive value of SII and SIRI for stroke prevalence was assessed through receiver operating characteristic (ROC) curve analysis, with the area under the ROC curve (AUC) being indicative of its predictive value. Additionally, clinical models including SIRI, coronary heart disease, hypertension, age, and poverty income ratio were constructed to evaluate their clinical applicability.ResultsBetween 1999 and 2018, 5,907 NHANES participants with asthma were identified, of which 199 participants experienced a stroke, while the remaining 5,708 participants had not. Spearman rank correlation analysis indicated that neither SII nor SIRI levels exhibited any significant correlation with the baseline characteristics of the participants (r

Breast cancer (BC) tissues have been proved to harbor microorganisms, which could potentially contribute to oncogenesis. Formalin-fixed paraffin-embedded (FFPE) tissues are the most widespread clinical samples in BC research. To verify the potential of FFPE tissues in microbiological analysis, we analyzed the microbial communities of FFPE and fresh frozen (FF) tumor samples from 30 participants diagnosed with BC deploying 16S rRNA sequencing. The operational taxonomic units (OTUs) analysis showed that 78.55% of OTUs in FFPE samples were consistent with FF samples. The composition of core bacteria did not change much, and there is also no difference in alpha diversity between FFPE and FF (without unclassified bacteria). Taxonomic variation results show that Firmicutes and Bacteroidota phyla, and their major classes, maintained the same proportion under two preservation methods. In addition, the major class Gammaproteobacteria, as well as its dominant orders Burkholderiales and Pseudomonadales all showed no significant difference in paired analysis. Moreover, the Proteobacteria and Actinobacteriota phyla showed no significant difference between FFPE and FF samples after subtracting unclassified bacteria. Therefore, premised with the intrinsic tumor heterogeneity and unclassified bacteria, there are potential values of FFPE tissues for intratumoral microbiome analysis in breast cancer.

BackgroundArterial stiffness is a significant determinant and evaluation of cardio-cerebrovascular disease and all-cause mortality risk in the stroke population. Estimated pulse wave velocity (ePWV) is a well-established indirect measure of arterial stiffness. We examined the association of ePWV with all-cause and cardio-cerebrovascular disease (CCD) mortality in the stroke population in a large sample of US adults.MethodsThe study design was a prospective cohort study with data from the National Health and Nutrition Examination Survey (NHANES) from 2003 to 2014, between the ages of 18–85 years, with follow-up through December 31, 2019. 1,316 individuals with stroke among 58,759 participants were identified and ultimately, 879 stroke patients were included in the analysis. ePWV was calculated from a regression equation using age and mean blood pressure according to the following formula: ePWV = 9.587 − (0.402 × age) + [4.560 × 0.001 × (age2)] − [2.621 × 0.00001 × (age2) × MBP] + (3.176 × 0.001 × age × MBP) − (1.832 × 0.01 × MBP). Survey-weighted Cox regression models were used to assess the association between ePWV and all-cause and CCD mortality risk.ResultsThe high ePWV level group had a higher increased risk of all-cause mortality and CCD mortality compared to the low ePWV level group after fully adjusting for covariates. With an increase in ePWV of 1 m/s, the risk of all-cause and CCD mortality increased by 44%–57% and 47%–72% respectively. ePWV levels were linearly correlated with the risk of all-cause mortality (P for nonlinear = 0.187). With each 1 m/s increase in ePWV, the risk of all-cause mortality increased by 44% (HR 1.44, 95% CI: 1.22–1.69; P

BackgroundEstimated pulse wave velocity (ePWV) has been proposed as a potential alternative to carotid-femoral pulse wave velocity to assess the degree of aortic stiffness, and may predict cardiovascular disease (CVD) outcomes and mortality in the general population. However, whether arterial stiffness estimated by ePWV predicts all-cause and cause-specific mortality in patients with diabetes mellitus (DM) has not been reported.MethodsThis was a prospective cohort study with data from the National Health and Nutrition Examination Survey (NHANES) from 1999 to 2014 and followed up until the end of December 2019. 5,235U.S. adults with DM (age≥20years) were included in the study. Arterial stiffness was estimated by ePWV. Survey-weighted Cox proportional hazards models were performed to assess the hazard ratios (HRs), and 95% confidence intervals (CIs) for the associations of ePWV with all-cause and cause-specific mortality. Meanwhile, the generalized additive model was used to visually assess the dose-dependent relationship between ePWV and mortality. As a complementary analysis, the relationship between mean blood pressure (MBP) and risk of mortality was also examined. Multiple imputations accounted for missing data.ResultsFor the 5,235 DM patients, the weighted mean age was 57.4 years, and 51.07% were male. During a median follow-up period of 115 months (interquartile range 81-155 months; 53,159 person-years), 1,604 all-cause deaths were recorded. In the fully adjusted Cox regression model, every 1 m/s increase in ePWV was associated with 56% (HR 1.56; 95% CI, 1.44 to 1.69) increase in the risk of all-cause. In addition, a nonlinear relationship between ePWV and all-cause mortality was observed (P for non-linear=0.033). Similar results were obtained after subgroup analysis and multiple imputations. Besides, the risk of most cause-specific mortality, except for accident and renal disease-specific mortality, increased from 53% to 102% for every 1 m/s increase in ePWV.ConclusionsIn the diabetic population, ePWV is independently associated with all-cause and most cause-specific mortality risks. ePWV may be a useful tool for assessing mortality risk.

Lipoxygenase 3 (LOX3) is a lipid peroxidase found in rice embryos that is known to affect seed quality. Interestingly, deletion of the LOX3 gene has been shown to improve rice seed quality but decrease resistance to rice blast disease and drought. To investigate these opposing effects, we generated a LOX3 knockout construct (ΔLox3) in rice (Oryza sativa L.) plants. Blast resistance and transcription levels of rice genes in ΔLox3 rice plants and the effects of exogenous jasmonic acid (JA) on resistance and transcriptional levels of rice genes in Magnaporthe oryzae-infected ΔLox3 rice plants were further elucidated. The results showed that the ΔLox3 plants exhibited normal phenotypes, with high levels of methyl-linolenate and reactive oxygen species (ROS), and the genes involved in three Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways contributed to rice seed quality. M. oryzae-infected ΔLox3 plants exhibited serious blast symptoms with a reduced defense response but increased ROS-mediated cell death, and the genes involved in seven KEGG pathways contributed to rice seed quality. Exogenous JA treatment alleviated blast symptoms in infected ΔLox3 plants by hindering hyphal expansion, inhibiting ROS-mediated cell death, and increasing the defense response, and genes involved in 12 KEGG pathways contributed to rice seed quality. These findings demonstrate that LOX3 plays an important role in rice growth and defense, and its knockout improves rice quality at the expense of disease resistance. Exogenous JA provides a means to compensate for the reduction in defense responses of LOX3 knockout rice lines, suggesting potential applications in agricultural production.

Microorganisms play a key role in ruminal digestion, some of which can be used as probiotics to promote growth in ruminants. However, which potential bacteria are responsible for ruminant growth and how they potentiate the basic mechanism is unclear. In this study, three bacterial strains, Bacillus pumilus (SN-3), Bacillus paralicheniformis (SN-6), and Bacillus altitudinis (SN-20) with multiple digestive enzymes were isolated from the rumen of healthy buffaloes. Among these strains, SN-6 secreted cellulase, laccase, and amylase, and significantly inhibited Staphylococcus aureus ATCC25923 and Escherichia coli K99 in vitro. In addition, SN-6 exhibited strong tolerance to artificial gastric juice, intestinal juice, and high temperature. Antibiotic resistance test, virulence gene test, and mouse toxicity test confirmed the safety of SN-6. Further, SN-6 significantly increased the body weight (p < 0.01), affects the intestinal microbiota structure, and alters the metabolomic patterns of Simmental. There was a remarkable difference in the β diversity of fecal microflora between SN-6 and control groups (p < 0.05). Furthermore, SN-6 significantly increased the abundance of Clostridium_sensu_stricto_1, Bifidobacterium, Blautia, and Cellulolyticum, decreased the relative abundance of Monoglobus and norank_f_Ruminococcacea. Moreover, SN-6 feeding significantly enriched intestinal metabolites (i.e., 3-indoleacrylic acid, kynurenic acid) to maintain intestinal homeostasis. Finally, the microbial and metabolic functional analysis indicated that SN-6 could enhance amino acid metabolism (mainly tryptophan metabolism) and lipid metabolism pathways. Overall, these findings indicated that SN-6 could be used as a probiotic in ruminants.

Boron (B) deficiency is an agricultural problem that causes significant yield losses in many countries. B transporters (BORs) are responsible for B uptake and distribution and play important roles in yield formation. A comprehensive analysis of the BOR family members in common wheat is still lacking. In the present study, to clarify the molecular characterization and response to B status, genome-wide TaBOR genes and expression patterns were investigated. Fourteen TaBOR genes were identified in common wheat by a homology search. The corresponding phylogenetic tree indicated that 14 TaBOR genes were separately classified into subfamilies of TaBOR1, TaBOR3, and TaBOR4. All TaBOR genes had 12–14 extrons and 11–13 introns. Most TaBOR proteins contained 10 conserved motifs, and motifs 1, 2, 3, 4, and 6 constituted the conserved bicarbonate (HCO3–) domain. Fourteen TaBOR genes were mapped on 13 chromosomes mainly distributed in the first, third, fifth, and seventh homologous groups. The promoters of TaBOR genes consisted of phytohormones, light responses, and stress-related cis-elements. GO analysis indicated that TaBOR genes were enriched in terms of transmembrane transport and ion homeostasis. TaBOR genes showed diverse expression profiles in different tissues. The members of the TaBOR1 subfamily showed high expression in grains, leaves, roots, stems, and spikes, but members of the TaBOR4 subfamily were highly expressed only in spikes and grains. RT–qPCR indicated that TaBOR1-5A, TaBOR1-5B, and TaBOR1-5D were induced by low B concentrations and had much higher expression in roots than in shoots. TaBOR3-3A, TaBOR3-3B, TaBOR3-3D, TaBOR4-1A, TaBOR4-1B, TaBOR4-1D, and TaBOR3-4B were induced by low and high B concentrations and had high expression in roots and shoots. TaBOR3-4D and TaBOR3-7B were upregulated by low and high B concentrations, respectively, but had expression only in roots. Our results provide basic information on the TaBOR family, which is beneficial for elucidating the functions of TaBOR genes to overcome the problem of B deficiency.

BackgroundsEctopic fat deposition is closely related to chronic kidney disease (CKD). Currently, there are few population studies that have been conducted to determine the relationship between renal parenchyma fat deposition and the risk of CKD among patients with type 2 diabetes mellitus (T2DM). Therefore, we employed magnetic resonance imaging (MRI) to detect renal parenchyma fat content in individuals with T2DM, expressed as renal fat fraction (FF), to explore whether renal FF is an important risk factor for CKD in patients with T2DM.MethodsIn this cross-sectional study, 189 subjects with T2DM were enrolled. CKD was defined as the estimated glomerular filtration rate (eGFR)

BackgroundIndividual lifestyle varies in the real world, and the comparative efficacy of lifestyles to preserve renal function remains indeterminate. We aimed to systematically compare the effects of lifestyles on chronic kidney disease (CKD) incidence, and establish a lifestyle scoring system for CKD risk identification.MethodsUsing the data of the UK Biobank cohort, we included 470,778 participants who were free of CKD at the baseline. We harnessed the light gradient boosting machine algorithm to rank the importance of 37 lifestyle factors (such as dietary patterns, physical activity (PA), sleep, psychological health, smoking, and alcohol) on the risk of CKD. The lifestyle score was calculated by a combination of machine learning and the Cox proportional-hazards model. A CKD event was defined as an estimated glomerular filtration rate 4 cups/day, biscuit cereal, low drink temperature, and processed meat, which have scored −12, −9, −7, −4, and −3, respectively. In restricted cubic spline regression analysis, a higher lifestyle score was associated with a lower risk of CKD event (p for linear relation < 0.001). Compared to participants with the lifestyle score < 0, participants scoring 0–20, 20–40, 40–60, and >60 exhibited 25, 42, 55, and 70% lower risk of CKD event, respectively. The C-statistic of the age-adjusted lifestyle score for predicting CKD events was 0.710 (0.703–0.718).ConclusionA lifestyle scoring system for CKD prevention was established. Based on the system, individuals could flexibly choose healthy lifestyles and avoid unhealthy lifestyles to prevent CKD.

Group I chitin deacetylases (CDAs), CDA1 and CDA2, play an essential role in cuticle formation and molting in the process of insect wing development. A recent report showed that trachea are able to take up a secreted CDA1 (serpentine, serp) produced in the fat body to support normal tracheal development in the fruit fly Drosophila melanogaster. However, whether CDAs in wing tissue were produced locally or derived from the fat body remains an open question. To address this question, we applied tissue-specific RNAi against DmCDA1 (serpentine, serp) and DmCDA2 (vermiform, verm) in the fat body or the wing and analyzed the resulting phenotypes. We found that repression of serp and verm in the fat body had no effect on wing morphogenesis. RT-qPCR showed that RNAi against serp or verm in the fat body autonomously reduced their expression levels of serp or verm in the fat body but had no non-autonomous effect on the expression in wings. Furthermore, we showed that inhibition of serp or verm in the developing wing caused wing morphology and permeability deficiency. Taken together, the production of Serp and Verm in the wing was autonomous and independent of the fat body.

Background and ObjectivesThe study aimed to evaluate the performance of a predictive model using the kidney failure risk equation (KFRE) for end-stage renal disease (ESRD) in diabetes and to investigate the impact of glomerular filtration rate (GFR) as estimated by different equations on the performance of the KFRE model in diabetes.Design, Setting, Participants, and MeasurementsA total of 18,928 individuals with diabetes without ESRD history from the UK Biobank, a prospective cohort study initiated in 2006–2010, were included in this study. Modification of diet in renal disease (MDRD), chronic kidney disease epidemiology collaboration (CKD-EPI) or revised Lund–Malmö (r-LM) were used to estimate GFR in the KFRE model. Cox proportional risk regression was used to determine the correlation coefficients between each variable and ESRD risk in each model. Harrell’s C-index and net reclassification improvement (NRI) index were used to evaluate the differentiation of the models. Analysis was repeated in subgroups based on albuminuria and hemoglobin A1C (HbA1c) levels.ResultsOverall, 132 of the 18,928 patients developed ESRD after a median follow-up of 12 years. The Harrell’s C-index based on GFR estimated by CKD-EPI, MDRD, and r-LM was 0.914 (95% CI = 0.8812–0.9459), 0.908 (95% CI = 0.8727–0.9423), and 0.917 (95% CI = 0.8837–0.9496), respectively. Subgroup analysis revealed that in diabetic patients with macroalbuminuria, the KFRE model based on GFR estimated by r-LM (KFRE-eGFRr-LM) had better differentiation compared to the KFRE model based on GFR estimated by CKD-EPI (KFRE-eGFRCKD-EPI) with a KFRE-eGFRr-LM C-index of 0.846 (95% CI = 0.797–0.894, p = 0.025), while the KFRE model based on GFR estimated by MDRD (KFRE-eGFRMDRD) showed no significant difference compared to the KFRE-eGFRCKD-EPI (KFRE-eGFRMDRD C-index of 0.837, 95% CI = 0.785–0.889, p = 0.765). Subgroup analysis of poor glycemic control (HbA1c >8.5%) demonstrated the same trend. Compared to KFRE-eGFRCKD-EPI (C-index = 0.925, 95% CI = 0.874–0.976), KFRE-eGFRr-LM had a C-index of 0.935 (95% CI = 0.888–0.982, p = 0.071), and KFRE-eGFRMDRD had a C-index of 0.925 (95% CI = 0.874–0.976, p = 0.498).ConclusionsIn adults with diabetes, the r-LM equation performs better than the CKD-EPI and MDRD equations in the KFRE model for predicting ESRD, especially for those with macroalbuminuria and poor glycemic control (HbA1c >8.5%).

Overlapping coding regions balance selective forces between multiple genes. One possible division of nucleotide sequence is that the predominant selective force on a particular nucleotide can be attributed to just one gene. While this arrangement has been observed in regions in which one gene is structured and the other is disordered, we sought to explore how overlapping genes balance constraints when both protein products are structured over the same sequence. We use a combination of sequence analysis, functional assays, and selection experiments to examine an overlapped region in HIV-1 that encodes helical regions in both Env and Rev. We find that functional segregation occurs even in this overlap, with each protein spacing its functional residues in a manner that allows a mutable non-binding face of one helix to encode important functional residues on a charged face in the other helix. Additionally, our experiments reveal novel and critical functional residues in Env and have implications for the therapeutic targeting of HIV-1.

ObjectivesPrimary aldosteronism (PA) is characterized by the autonomous excessive production of aldosterone in the adrenal cortex. Aldosterone is associated with damages to heart muscle and skeletal muscle. The purpose of this study was to evaluate serum levels of muscle injury markers and their associated factors in patients with primary aldosteronism.MethodsWe retrospectively enrolled subjects with PA and essential hypertension (EH) who had completed testing for serum high sensitivity troponin T (hs-TnT), creatine kinase isoenzyme MB (CK-MB) and myoglobin from the database of the Chongqing Primary Aldosteronism Study (CONPASS). Univariate and multivariate linear regression analyses were performed to analyze the influencing factors of myocardial injury markers.ResultsIn total, 278 patients with PA and 445 patients with EH were enrolled in this study. Compared with EH patients, serum concentrations of hs-TnT [7.0 (4.0–12.0) vs. 6.0 (3.0–11.0) ng/L; p=0.005] and myoglobin [24.2 (21.0–38.1) vs. 21.8 (21.0–31.9) μg/L; p=0.023] were significantly higher among PA patients, while no significant difference of CK-MB was found between two groups [1.4 (1.0–2.0) vs. 1.3 (0.9–1.9) μg/L; p=0.154]. Univariate linear regression analysis showed that myoglobin was negatively correlated with serum potassium (β=-0.31; p

Background While both renin‐dependent and renin‐independent aldosterone secretion contribute to aldosteronism, their relative associations with cardiovascular disease (CVD) risk has not been investigated. Methods and Results A total of 2909 participants from the FOS (Framingham Offspring Study) with baseline, serum aldosterone concentration, and plasma renin concentration who attended the sixth examination cycle and were followed up until 2014 and who were free of CVD were included. We further recruited 2612 hypertensive participants from the CONPASS (Chongqing Primary Aldosteronism Study). Captopril challenge test was performed to confirm renin‐dependent or ‐independent aldosteronism in CONPASS. Among 1433 hypertensive subjects of FOS, when compared with those with serum aldosterone concentration 15 mIU L−1 (identified as renin‐dependent aldosteronism) showed an unchanged CVD risk. In CONPASS, renin‐independent aldosteronism carried a significantly higher risk of CVD than normal aldosterone (odds ratio, 2.57 [95% CI, 1.13–5.86]), while the CVD risk remained unchanged in renin‐dependent aldosteronism. Elevation of the urinary potassium‐to‐sodium excretion ratio, reflective of mineralocorticoid receptor activity, was only observed in participants with renin‐independent aldosteronism. Conclusions Among patients with hypertension, renin‐independent aldosteronism is more closely associated with CVD risk than renin‐dependent aldosteronism.

BackgroundAdrenocorticotropic hormone (ACTH) is widely used in adrenal vein sampling (AVS) and can be administered as a bolus injection or continuous infusion. The optimal administration method has not been determined. We aimed to compare the effects of ACTH bolus with infusion on cannulation success, lateralization assessment and adverse events (AEs).MethodsRetrospectively collected data from patients with primary aldosteronism who underwent AVS with ACTH at a tertiary hospital in China. Rate of successful cannulation, lateralization index (LI), complete biochemical remission and AEs related to AVS were analyzed.ResultsThe study included 80 patients receiving ACTH bolus and 94 receiving infusions. The rate of successful cannulation was comparable between bolus and infusion groups (75/80, 93.4% vs 88/94, 93.6%). In those with successful cannulation, the bolus group had a higher selectivity index than the infusion group, while LI [6.4(1.8-17.5) vs. 7.6(2.0-27.8), P=0.48] and rate of complete biochemical remission (43/44, 97.7% vs 53/53, 100%, P=0.45) did not significantly differ between the two groups. One in the bolus and one patient in the infusion group had adrenal vein rupture but they recovered with conservative treatment. The bolus group reported more transient AEs such as palpitation (52.9% vs 2.2%) and abdominal discomfort (40.0% vs 2.2%) than the infusion group.ConclusionsDue to their similar effects on cannulation success and lateralization, but a lower rate of transient AEs in the infusion group, the continuous infusion method should be recommended for ACTH stimulation in AVS.

It is significant for anesthesiologists to have a precise grasp of the recovery time of the patient after anesthesia. Accurate prediction of anesthesia recovery time can support anesthesiologist decision-making during surgery to help reduce the risk of surgery in patients. However, effective models are not proposed to solve this problem for anesthesiologists. In this paper, we seek to find effective forecasting methods. First, we collect 1824 patient anesthesia data from the eye center and then performed data preprocessing. We extracted 85 variables to predict recovery time from anesthesia. Second, we extract anesthesia information between variables for prediction using machine learning methods, including Bayesian ridge, lightGBM, random forest, support vector regression, and extreme gradient boosting. We also design simple deep learning models as prediction models, including linear residual neural networks and jumping knowledge linear neural networks. Lastly, we perform a comparative experiment of the above methods on the dataset. The experiment demonstrates that the machine learning method performs better than the deep learning model mentioned above on a small number of samples. We find random forest and XGBoost are more efficient than other methods to extract information between variables on postoperative anesthesia recovery time.

TiO2 films exhibiting structural colors were successfully prepared using one-step electrochemical oxidation. Results of theoretical analyses and digital simulations revealed that the structural color of a TiO2 thin film could be regulated by adjusting oxidation voltage and oxidation time with different oxidation voltages leading to changes in structural color annulus number. At a low oxidation voltage, each thin film exhibited a single structural color, while thin films with different structural colors were obtained by varying the oxidation time. By contrast, at a higher oxidation voltage, each film exhibited iridescent and circular structural color patterns associated with symmetrical decreases in surface oxidation current density along radial lines emanating from the film center to its outer edges. TiO2 films exhibiting iridescent structural colorations have broad application prospects in industrial fields related to photocatalysis and photovoltaic cells.

Traffic flow forecasting is challenging for us to analyze intricate spatial–temporal dependencies and obtain incomplete information of spatial–temporal connection. Existing frameworks mostly construct spatial and temporal modeling based on a fixed graph structure and given time series. However, a fixed adjacency matrix is limited to learn effective spatial–temporal correlations of the network because it represents incomplete information for missing genuine relation. To solve the difficulty, we design a novel spatial–temporal adaptive fusion graph network (STFAGN) for traffic prediction. First, our model combines fusion convolution layers with a novel adaptive dependency matrix by end-to-end training to capture the hidden spatial-temporal dependency on the data to complete incomplete information. Second, STFAGN could, in parallel, acquire hidden spatial–temporal dependencies by a fusion operation and temporal trend by fast-DTW. Meanwhile, we use ReZero connection as a simple change of deep residual networks to facilitate deep signal propagation and faster converge. Lastly, we conduct comparative experiments on two public traffic network datasets, whose results demonstrate the superiority of our algorithm compared to state-of-the-art baseline types. Ablation experiments also prove the rationality of the framework of STFAGN.

The vascular bundle is an important structural unit that determines the growth and properties of bamboo. A high-resolution X-ray microtomography (μCT) was used to observe and reconstruct a three-dimensional (3D) morphometry model of the vascular bundle of the Qiongzhuea tumidinoda node due to its advantages of quick, nondestructive, and accurate testing of plant internal structure. The results showed that the morphology of vascular bundles varied significantly in the axial direction. In the cross-section, the number of axial vascular bundles reached a maximum at the lower end of the sheath scar, and the minimum of it was at the middle of the diaphragm. The frequency of axial vascular bundles decreased from the lower end of the node to the nodal ridge, and subsequently increased until the upper end of the bamboo node. The proportion of parenchyma, fibers, and conducting tissue was 65.7%, 30.5%, and 3.8%, respectively. The conducting tissues were intertwined to form a complex 3D network structure, with a connectivity of 94.77%. The conducting tissue with the largest volume accounted for 60.26% of the total volume of the conducting tissue. The 3D-distribution pattern of the conducting tissue of the node and that of the fibers were similar, but their thickness changed in the opposite pattern. This study revealed the 3D morphometry of the conducting tissue and fibers of the bamboo node, the reconstruction of the skeleton made the morphology more intuitive. Quantitative indicators such as the 3D volume, proportion, and connectivity of each type of tissue was obtained, the bamboo node was enlarged mainly caused by the particularly developed fibers. This work laid the foundation for a better understanding of the mechanical properties and water transportation of bamboo and revealed the mystery of bamboo node shedding of Q. tumidinoda.

The mechanical performance of bamboo is highly dependent on its structural arrangement and the properties of biomacromolecules within the cell wall. The relationship between carbohydrates topochemistry and gradient micromechanics of multilayered fiber along the diametric direction was visualized by combined microscopic techniques. Along the radius of bamboo culms, the concentration of xylan within the fiber sheath increased, while that of cellulose and lignin decreased gradually. At cellular level, although the consecutive broad layer (Bl) of fiber revealed a relatively uniform cellulose orientation and concentration, the outer Bl with higher lignification level has higher elastic modulus (19.59–20.31 GPa) than that of the inner Bl close to the lumen area (17.07–19.99 GPa). Comparatively, the cell corner displayed the highest lignification level, while its hardness and modulus were lower than that of fiber Bl, indicating the cellulose skeleton is the prerequisite of cell wall mechanics. The obtained cytological information is helpful to understand the origin of the anisotropic mechanical properties of bamboo.

Roses are the most important cut flower crops and widely used woody ornamental plants in gardens throughout the world, and they are model plants for studying the continuous-flowering trait of woody plants. To analyze the molecular regulation mechanism of continuous flowering, comparative transcriptome data of once- and continuous-flowering roses in our previous study were used to conduct weighted gene co-expression network analysis (WGCNA) to obtain the candidate genes related to flowering transitions. The expression patterns of candidate genes at different developmental stages between Rosa chinensis “Old Blush” (continuous-flowering cultivar) and R. “Huan Die” (once-flowering cultivar) were investigated, and the relationship of the key gene with the endogenous hormone was analyzed. The results showed that the expression trends of VIN3-LIKE 1 (VIL1), FRIGIDA- LIKE 3 (FRI3), APETALA 2- LIKE (AP2-like) and CONSTANS-LIKE 2 (CO-like 2) genes were significantly different between “Old Blush” and “Huan Die”, and the expression trends of SUPPRESSOR OF OVEREXPRESSION OF CONSTANS1 (SOC1) and CO-like 2 were consistent in the flowering transition of “Old Blush” under different environments. The changes in cytokinin and gibberellic acid (GA3) content were different in the two rose cultivars. The overall change trend of the abscisic acid and GA3 in the flowering transition of “Old Blush” under different environments was consistent. The promoter sequence of CO-like 2 contained a P-box element associated with gibberellin response, as well as binding sites for transcription factors. In a word, we found CO-like 2 associated with continuous flowering and some factors that may synergistically regulate continuous flowering. The results provided a reference for elucidating the molecular regulatory mechanisms of continuous-flowering traits in roses.

Background: Significant evidence suggests that asthma might originate from low-grade systemic inflammation. Previous studies have established a positive association between the systemic immune-inflammation index (SII) and the systemic inflammation response index (SIRI) levels and the risk of stroke. However, it remains unclear whether SII, SIRI and the prevalence of stroke are related in individuals with asthma. Methods: The present cross-sectional study used data from the National Health and Nutrition Examination Survey (NHANES) conducted between 1999 and 2018. SII was calculated using the following formula: (platelet count × neutrophil count)/lymphocyte count. SIRI was calculated using the following formula: (neutrophil count × monocyte count)/lymphocyte count. The Spearman rank correlation coefficient was used to determine any correlation between SII, SIRI, and the baseline characteristics. Survey-weighted logistic regression was employed to calculate odds ratios (ORs) and 95% confidence intervals (CIs) to determine the association between SII, SIRI, and stroke prevalence. The predictive value of SII and SIRI for stroke prevalence was assessed through receiver operating characteristic (ROC) curve analysis, with the area under the ROC curve (AUC) being indicative of its predictive value. Additionally, clinical models including SIRI, coronary heart disease, hypertension, age, and poverty income ratio were constructed to evaluate their clinical applicability Results: Between 1999 and 2018, 5,907 NHANES participants with asthma were identified, of which 199 participants experienced a stroke, while the remaining 5,708 participants had not. Spearman rank correlation analysis indicated that neither SII nor SIRI levels exhibited any significant correlation with the baseline characteristics of the participants (r<0.1). ROC curves were used to determine the optimal cut-off values for SII and SIRI levels to classify participants into low- and high-level groups. Higher SII and SIRI levels were associated with a higher prevalence of stroke, with ORs of 1.80 (95% CI, 1.18-2.76) and 2.23 (95% CI, 1.39-3.57), respectively. The predictive value of SIRI (AUC=0.618) for stroke prevalence was superior to that of SII (AUC=0.552). Furthermore, the clinical model demonstrated good predictive value (AUC=0.825), with a sensitivity of 67.1% and specificity of 87.7%. Conclusion: In asthmatics, higher levels of SII and SIRI significantly increased the prevalence of stroke, with its association being more pronounced in individuals with coexisting obesity and hyperlipidaemia. SII and SIRI are relatively stable novel inflammatory markers in the asthmatic population, with SIRI having a better predictive value for stroke prevalence than SII. [ABSTRACT FROM AUTHOR]