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Abstract Background Malnutrition is common in patients with chronic cardiovascular disease and is associated with significantly higher all-cause mortality. Approximately one-third of patients with heart failure are malnourished. However, the relationship between malnutrition and idiopathic pulmonary arterial hypertension (IPAH) remains unclear. This study aimed to clarify the prognostic value of malnutrition in patients with IPAH. Methods A total of 432 consecutive participants with IPAH were included in this study between March 2013 and August 2021. Three common malnutrition assessment tools, including the geriatric nutritional risk index (GNRI), prognostic nutritional index (PNI), and controlling nutritional status (CONUT) score, were used to evaluate the nutritional status of patients with IPAH. The relationships between the malnutrition tools and long-term adverse outcomes were determined using restricted cubic splines and multivariate Cox regression models. Results During a mean follow-up of 3.1 years, 158 participants experienced clinical worsening or all-cause death. Patients were stratified into the low-, intermediate- and high-risk groups based on the European Society of Cardiology (ESC) risk stratification, and the PNI (55.9 ± 5.7 vs. 54.4 ± 7.2 vs. 51.1 ± 7.1, P = 0.005) and CONUT score (2.1 ± 0.9 vs. 2.5 ± 1.2 vs. 3.3 ± 1.1, P

As modern communication technology advances apace, the digital communication signals identification plays an important role in cognitive radio networks, the communication monitoring and management systems. AI has become a promising solution to this problem due to its powerful modeling capability, which has become a consensus in academia and industry. However, because of the data-dependence and inexplicability of AI models and the openness of electromagnetic space, the physical layer digital communication signals identification model is threatened by adversarial attacks. Adversarial examples pose a common threat to AI models, where well-designed and slight perturbations added to input data can cause wrong results. Therefore, the security of AI models for the digital communication signals identification is the premise of its efficient and credible applications. In this paper, we first launch adversarial attacks on the end-to-end AI model for automatic modulation classification, and then we explain and present three defense mechanisms based on the adversarial principle. Next we present more detailed adversarial indicators to evaluate attack and defense behavior. Finally, a demonstration verification system is developed to show that the adversarial attack is a real threat to the digital communication signals identification model, which should be paid more attention in future research.

Abstract Background Insulin resistance (IR) plays an important role in the pathophysiology of cardiovascular disease. Recent studies have shown that diabetes mellitus and impaired lipid metabolism are associated with the severity and prognosis of idiopathic pulmonary arterial hypertension (IPAH). However, the relationship between IR and pulmonary hypertension is poorly understood. This study explored the association between four IR indices and IPAH using data from a multicenter cohort. Methods A total of 602 consecutive participants with IPAH were included in this study between January 2015 and December 2022. The metabolic score for IR (METS-IR), triglyceride to high-density lipoprotein cholesterol (TG/HDL-C) ratio, triglyceride and glucose (TyG) index, and triglyceride-glucose-body mass index (TyG-BMI) were used to quantify IR levels in patients with IPAH. The correlation between non-insulin-based IR indices and long-term adverse outcomes was determined using multivariate Cox regression models and restricted cubic splines. Results During a mean of 3.6 years’ follow-up, 214 participants experienced all-cause death or worsening condition. Compared with in low to intermediate-low risk patients, the TG/HDL-C ratio (2.9 ± 1.7 vs. 3.3 ± 2.1, P = 0.003) and METS-IR (34.5 ± 6.7 vs. 36.4 ± 7.5, P

Abstract Background Patients with pulmonary arterial hypertension (PAH) exhibit a distinct gut microbiota profile; however, the causal association between gut microbiota, associated metabolites, and PAH remains elusive. We aimed to investigate this causal association and to explore whether dietary patterns play a role in its regulation. Methods Summary statistics of gut microbiota, associated metabolites, diet, and PAH were obtained from genome-wide association studies. The inverse variance weighted method was primarily used to measure the causal effect, with sensitivity analyses using the weighted median, weighted mode, simple mode, MR pleiotropy residual sum and outlier (MR-PRESSO), and MR-Egger methods. A reverse Mendelian randomisation analysis was also performed. Results Alistipes (odds ratio [OR] = 2.269, 95% confidence interval [CI] 1.100–4.679, P = 0.027) and Victivallis (OR = 1.558, 95% CI 1.019–2.380, P = 0.040) were associated with an increased risk of PAH, while Coprobacter (OR = 0.585, 95% CI 0.358–0.956, P = 0.032), Erysipelotrichaceae (UCG003) (OR = 0.494, 95% CI 0.245–0.996, P = 0.049), Lachnospiraceae (UCG008) (OR = 0.596, 95% CI 0.367–0.968, P = 0.036), and Ruminococcaceae (UCG005) (OR = 0.472, 95% CI 0.231–0.962, P = 0.039) protected against PAH. No associations were observed between PAH and gut microbiota-derived metabolites (trimethylamine N-oxide [TMAO] and its precursors betaine, carnitine, and choline), short-chain fatty acids (SCFAs), or diet. Although inverse variance-weighted analysis demonstrated that elevated choline levels were correlated with an increased risk of PAH, the results were not consistent with the sensitivity analysis. Therefore, the association was considered insignificant. Reverse Mendelian randomisation analysis demonstrated that PAH had no causal impact on gut microbiota-derived metabolites but could contribute to increased the levels of Butyricicoccus and Holdemania, while decreasing the levels of Clostridium innocuum, Defluviitaleaceae UCG011, Eisenbergiella, and Ruminiclostridium 5. Conclusions Gut microbiota were discovered suggestive evidence of the impacts of genetically predicted abundancy of certain microbial genera on PAH. Results of our study point that the production of SCFAs or TMAO does not mediate this association, which remains to be explained mechanistically.

Abstract Aims Despite refinements in balloon pulmonary angioplasty (BPA), total occlusion remains a challenge in chronic thromboembolic pulmonary hypertension (CTEPH). Owing to their low success and high complication rates, most interventional cardiologists are reluctant to address total occlusion, and there is a paucity of literature on BPA performance in total occlusion. We aimed to classify total occlusion according to morphology and present an illustrative approach for devising a tailored treatment strategy for each distinct type of total occlusion. Methods and results All patients diagnosed with CTEPH who underwent BPA between May 2018 and May 2022 at Fuwai Hospital in Beijing, China, were included retrospectively. A total of 204 patients with CTEPH who underwent BPA were included in this study. Among these, 38 occluded lesions were addressed in 33 patients. Based on the morphology, we categorized the lesions into three groups: pointed‐head, round‐head, and orifice occlusions. Pointed‐head occlusion could be successfully addressed using soft‐tip wire, round‐head occlusion warranted hard‐tip wire and stronger backup, and orifice occlusion warranted the strongest backup force. The success rates for each group were as follows: pointed‐head (95.45%), round‐head (46.15%), and orifice occlusion (33.33%), with orifice occlusion having the highest complication rate (50%). The classification of occlusion was associated with BPA success (round‐head occlusion vs. pointed‐head occlusion, OR 24.500, 95% CI 2.498–240.318, P = 0.006; orifice occlusion vs. pointed‐head occlusion, OR 42.000, 95% CI 3.034–581.434, P = 0.005). Conclusions Occlusion morphology has a significant impact on BPA success and complication rates. A treatment strategy tailored to each specific occlusive lesion, as outlined in the present study, has the potential to serve as a valuable guide for clinical practitioners.

Amanita phalloides poisoning, renowned for its high mortality rates, is one of the most serious food safety issue in certain regions worldwide. Assessment of prognosis and development of more efficacious therapeutic strategies are critical importance for amanita phalloides poisoning patients. The aim of the study is to establish a nomogram to predict the clinical outcome of amanita phalloides poisoning patients based on the independent risk factor for prognosis. Herein, between January 2013 and September 2023, a cohort of 149 patients diagnosed with amanita phalloides poisoning was enrolled and randomly allocated into training and validation cohorts, comprising 102 and 47 patients, respectively. Multivariate logistic regression analysis was performed to identify the independent risk factors for morality of amanita phalloides poisoning patients in training cohort. Subsequently, a nomogram model was constructed to visually display the risk prediction model. The predictive accuracy of nomogram was verified by the validation cohort. The C index, the area under the receiver operating characteristic curve (AUC), and calibration plots were used to assessed the performance of nomogram. The clinical utility was evaluated by decision curve analysis (DCA). In the present study, the results showed that hepatic encephalopathy (HE), upper gastrointestinal bleeding (UGB), AST, and PT were the independent risk factors associated with the mortality of amantia phalloides poisoning patients. We constructed a new nomogram to evaluate the probability of death induced by amantia phalloides poisoning. The AUC for the prediction accuracy of the nomogram was 0.936 for the training cohort and 0.929 for the validation cohort. The calibration curves showed that the predicted probability matched the actual likelihood. The results of the DCA suggested that the nomogram has a good potential for clinical application. In summary, we developed a new nomogram to assess the probability of mortality for amanita phalloides poisoning patients. This nomogram might facilitate clinicians in making more efficacious treatment strategies for patients with amanita phalloides poisoning.

Excessive residue of metronidazole (MNZ) in food is harmful to the human body. There is an urgent demand to develop a portable tool for MNZ detection on-site. In this study, fifteen aptamers were prepared through targeted base mutation. Apt1-3 with the highest enrichment was chosen for further study. Its affinity was characterized by molecular docking simulation, AuNPs colorimetric assay, graphene oxide (GO) fluorescence assay, and exonuclease assay. Kd was determined by GO fluorescence assay (Kd: 92.60 ± 25.59 nM). Its specificity was also characterized by an exonuclease assay. A novel aptasensor was constructed by using the newly identified aptamer combined with the smartphone dark box. The principle of color change is caused by the aggregation state of AuNPs. Smartphones act as reading instruments. The detection can be completed in just a few seconds without the aid of instruments, achieving a detection limit of 0.15 nmol/mL and a range of 6.7–44.4 nmol/mL (R2 = 0.9810). Therefore, the constructed smartphone colorimetric sensor based on mutant aptamers has important applications in food detection.

Abstract Objective To compare the clinical effects of intramedullary elastic reduction of the “de-sharpened Kirschner wire and traditional three-dimensional manipulation in the treatment of Gartland type III posterolateral supracondylar fracture of the humerus in children. Methods A retrospective cohort analysis was made on 106 cases of Gartland type III posterolateral supracondylar fracture of the humerus treated in the Department of Orthopaedics of a Children’s Hospital from March 2020 to March 2022. According to different surgical technology, the patients were divided into two groups: intramedullary elastic reduction of the de-sharpened Kirschner wire group (experimental group, n = 50) and traditional three-dimensional manipulation group (control group, n = 56). The surgical operating time, intraoperative fluoroscopy times, postoperative Baumann angle changes, postoperative elbow function Flynn score, and complications were collected and compared between the two groups. Results All the enrolled cases underwent surgery successfully and were followed-up at least 6 months. The surgical operating time of the experimental group was 32.88 ± 3.69 min and that of the control group was 45.56 ± 10.13 min, and the difference was statistically significant (P 0.5). There were no complications such as osteomyelitis, compartment syndrome, iatrogenic vascular and nerve injury, and myositis ossificans in either group. Conclusions Good functional outcome can be obtained with both intramedullary elastic reduction of the de-sharpened Kirschner wire and traditional three-dimensional manipulation for Gartland type III posterolateral displaced supracondylar fracture of the humerus in children; however, the former does not need repeated manipulation, and the operation time is shorter, the number of intraoperative fluoroscopy is less, and the recovery of the Baumann angle is better.

Abstract Aims Left ventricular (LV) remodelling after acute myocardial infarction (AMI) is associated with heart failure and increased mortality. There was no consensus on the definition of LV remodelling, and the prognostic value of LV remodelling with different definitions has not been compared. We aimed to find the optimal definition and develop a prediction nomogram as well as online calculator that can identify patients at risk of LV remodelling. Methods and results This prospective, observational study included 829 AMI patients undergoing percutaneous coronary intervention from January 2015 to January 2020. Echocardiography was performed within the 48 h of admission and at 6 months after infarction to evaluate LV remodelling, defined as a 20% increase in LV end‐diastolic volume (LVEDV), a 15% increase in LV end‐systolic volume (LVESV), or LV ejection fraction (LVEF)

Abstract Inflammation contributes to development of idiopathic pulmonary arterial hypertension (IPAH), and tumor biomarkers can reflect inflammatory and immune status. We aimed to determine the value of tumor biomarkers in IPAH comprehensively. We enrolled 315 patients with IPAH retrospectively. Tumor biomarkers were correlated with established indicators of pulmonary hypertension severity. Multivariable Cox regression found that AFP (hazard ratio [HR]: 1.587, 95% confidence interval [CI]: 1.014–2.482, p = 0.043) and CA125 (HR: 2.018, 95% CI: 1.163–3.504, p = 0.013) could independently predict prognosis of IPAH. The changes of AFP over time were associated with prognosis of patients, each 1 ng/mL increase in AFP was associated with 5.4% increased risk of clinical worsening (HR: 1.054, 95% CI: 1.001–1.110, p = 0.046), enabling detection of disease progression. Moreover, beyond well‐validated PH biomarkers, CA125 was still of prognostic value in the low‐risk patients (HR: 1.014, 95% CI: 1.004–1.024, p = 0.004), allowing for more accurate risk stratification and prediction of disease outcomes. AFP and CA125 can serve for prognosis prediction, risk stratification, and dynamic monitor in patients with IPAH.

Background: Balloon pulmonary angioplasty (BPA) is typically performed in a sequential manner. Objectives: This study aimed to determine the lowest frequency of BPA for patients who could not reach treatment goals in a short period. Design: Retrospective cohort. Methods: We retrospectively enrolled 186 BPA-treated patients diagnosed with chronic thromboembolic pulmonary hypertension. According to the accumulative number of performed BPA sessions or treated pulmonary vessels or the ratio of the number of treated pulmonary vessels/the number of baseline lesions (T/P) prior to the initial occurrence of clinical outcome or censored date, we divided patients into different groups. The principal outcome was clinical worsening. Results: After stratifying patients by the number of performed BPA sessions, most baseline parameters were comparable among groups. During follow-up, 31 (16.7%) of 186 patients experienced clinical worsening. The 6-month cumulative clinical worsening-free survival rates of ⩾2 performed sessions group were significantly higher than that of 1 performed session group. The 12-month cumulative rates of clinical worsening-free survival exhibited a declining pattern in the subsequent sequence: ⩾3, 2, and 1 performed BPA sessions, and this trend persisted when follow-up time exceeded 12 months. The 6-, 12-, and 24-month cumulative clinical worsening-free survival rates were comparable between patients with 3 and ⩾4 performed BPA sessions. Similar results were also observed when stratifying patients by the accumulative number of treated pulmonary vessels (⩽8, 9–16, ⩾17) and T/P (⩽0.789, 0.790–1.263, ⩾1.264). Conclusion: To achieve optimal short-term outcomes, patients might need to undergo ⩾2 BPA sessions or have ⩾9 pulmonary vessels treated or have T/P ⩾0.790 within 6 months, and undergo ⩾3 BPA sessions or have ⩾17 pulmonary vessels treated or have T/P ⩾1.264 within 12 months.

For individuals with celiac disease (CD), the current clinical therapy option available is a lifelong gluten-free diet. Therefore, it is essential to swiftly and efficiently detect gluten in foods. A colorimetric sensor has been developed, which operates by regulating the aggregation and dispersion state of AuNPs induced by high concentration NaCl through the specific binding of gliadin and aptamer, thereby achieving rapid detection of gliadin in flour. It is found that the sensor exhibits good linearity in the concentration range of 0.67–10 μM and the LOD (3σ/S) is 12 nM. And it can accurately distinguish various types of free-gliadin samples, with a spiked recovery rate of 85%–122.3%. To make the detection process more convenient, the colorimetric results of the biosensor were translated into RGB color-gamut parameters by a smartphone color-picking program for further analysis. Gliadin can still be accurately quantified with the established smartphone platform, and a correlation coefficient of 0.988 was found. The proposed portable smartphone aptamer colorimetric sensing device has achieved satisfactory results in the rapid detection of gliadin in food.

Adipose tissue is the site of long-term energy storage. During the fasting state, exercise, and cold exposure, the white adipose tissue mobilizes energy for peripheral tissues through lipolysis. The mobilization of lipids from white adipose tissue to the liver can lead to excess triglyceride accumulation and fatty liver disease. Although the white adipose tissue is known to release free fatty acids, a comprehensive analysis of lipids mobilized from white adipocytes in vivo has not been completed. In these studies, we provide a comprehensive quantitative analysis of the adipocyte-secreted lipidome and show that there is interorgan crosstalk with liver. Our analysis identifies multiple lipid classes released by adipocytes in response to activation of lipolysis. Time-dependent analysis of the serum lipidome showed that free fatty acids increase within 30 min of β3-adrenergic receptor activation and subsequently decrease, followed by a rise in serum triglycerides, liver triglycerides, and several ceramide species. The triglyceride composition of liver is enriched for linoleic acid despite higher concentrations of palmitate in the blood. To further validate that these findings were a specific consequence of lipolysis, we generated mice with conditional deletion of adipose tissue triglyceride lipase exclusively in adipocytes. This loss of in vivo adipocyte lipolysis prevented the rise in serum free fatty acids and hepatic triglycerides. Furthermore, conditioned media from adipocytes promotes lipid remodeling in hepatocytes with concomitant changes in genes/pathways mediating lipid utilization. Together, these data highlight critical role of adipocyte lipolysis in interorgan crosstalk between adipocytes and liver.

Abstract Background Cystatin C is a novel biomarker to identify renal dysfunction and cardiovascular risk. Objective The aim of this study was to investigate the role of cystatin C in non-invasive risk prediction in a large cohort of patients with pre-capillary pulmonary hypertension (PH). Method We retrospectively analyzed pre-capillary PH patients with available cystatin C and hemodynamic data derived from right heart catheterization. Results A total of 398 consecutive patients with confirmed pre-capillary PH were recruited from Fuwai Hospital between November 2020 and November 2021. Over a median duration of 282 days, 72 (18.1%) of these patients experienced clinical worsening. Cystatin C levels significantly correlated with cardiac index (r = -0.286, P

Interplay between energy-storing white adipose cells and thermogenic beige adipocytes contributes to obesity and insulin resistance. Irrespective of specialized niche, adipocytes require the activity of the nuclear receptor PPARγ for proper function. Exposure to cold or adrenergic signaling enriches thermogenic cells though multiple pathways that act synergistically with PPARγ; however, the molecular mechanisms by which PPARγ licenses white adipose tissue to preferentially adopt a thermogenic or white adipose fate in response to dietary cues or thermoneutral conditions are not fully elucidated. Here, we show that a PPARγ/long noncoding RNA (lncRNA) axis integrates canonical and noncanonical thermogenesis to restrain white adipose tissue heat dissipation during thermoneutrality and diet-induced obesity. Pharmacologic inhibition or genetic deletion of the lncRNA Lexis enhances uncoupling protein 1–dependent (UCP1-dependent) and -independent thermogenesis. Adipose-specific deletion of Lexis counteracted diet-induced obesity, improved insulin sensitivity, and enhanced energy expenditure. Single-nuclei transcriptomics revealed that Lexis regulates a distinct population of thermogenic adipocytes. We systematically map Lexis motif preferences and show that it regulates the thermogenic program through the activity of the metabolic GWAS gene and WNT modulator TCF7L2. Collectively, our studies uncover a new mode of crosstalk between PPARγ and WNT that preserves white adipose tissue plasticity.

Rheumatoid arthritis (RA) is an autoimmune disease that can induce joint deformities and functional impairment, significantly impacting the overall well-being of individuals. Exosomes, which are cellularly secreted vesicles, possess favorable biological traits such as biocompatibility, stability, and minimal toxicity. Additionally, they contain nucleic acids, lipids, proteins, amino acids, and metabolites, serving as mediators in cellular communication and information exchange. Recent studies have demonstrated the association between exosomes and the pathogenesis of RA. Exosomes derived from mesenchymal stem cells, dendritic cells, and neutrophils exert influence on the biological functions of immune cells and joint cells, however, the precise mechanism remains largely unclarified. This comprehensive review systematically analyzes and summarizes the biological characteristics and functionalities of exosomes derived from diverse cellular sources, thus establishing a scientific foundation for the utilization of exosomes as diagnostic targets and therapeutic modalities in the context of RA.

ObjectiveTo construct an artificial intelligence system to measure acetabular index and evaluate its accuracy in clinical application.MethodsA total of 10,219 standard anteroposterior pelvic radiographs were collected retrospectively from April 2014 to December 2018 in our hospital. Of these, 9,219 radiographs were randomly selected to train and verify the system. The remaining 1,000 radiographs were used to compare the system's and the clinicians' measurement results. All plain pelvic films were labeled by an expert committee through PACS system based on a uniform standard to measure acetabular index. Subsequently, eight other clinicians independently measured the acetabular index from 200 randomly selected radiographs from the test radiographs. Bland–Altman test was used for consistency analysis between the system and clinician measurements.ResultsThe test set included 1,000 cases (2,000 hips). Compared with the expert committee measurement, the 95% limits of agreement (95% LOA) of the system was −4.02° to 3.45° (bias = −0.27°, P

Herein, the Ruthenium nanoparticles (NPs) with the size of 12 nm were decorated on the hexagonal prism silicalite-1 (Ru/S-1) by the gas bubbling-assisted membrane reduction method (GBMR). The adsorption/activation properties are improved for reactant molecules due to the formation of an interfacial structure that enhances the interaction between the Ru NPs and S-1. The Ru/S-1 catalyst displays the highest catalytic activity (T50 = 356 °C) and CO2 selectivity (SCO2m = 99.9%). Moreover, no obvious deactivation was observed over the Ru/S-1 catalyst even after five cycles, and the values of T50 and SCO2m after cycling five times are similar to the fresh catalyst. The Ru/S-1 catalyst with excellent catalytic performance can be compared with a series of noble metal catalysts for soot oxidation. The catalytic mechanism of the Ru/S-1 catalyst was revealed by in situ characterization for soot oxidation. The interfacial effect between Ru NPs and S-1 plays an important role in the conversion of NO to NO2 during soot oxidation. Preparation of Ru/S-1 catalyst provides a hopeful way to obtain considerably low-cost and highly stable auto-exhaust treatment catalysts.

Abstract Aims Contrast‐induced nephropathy remains a common complication of coronary procedure and increases poor outcomes, especially in patients with heart failure. Plasma volume expansion relates to worsening prognosis of heart failure. We hypothesized that calculated plasma volume status (PVS) might provide predictive utility for contrast‐induced nephropathy in patients with heart failure undergoing elective percutaneous coronary intervention (PCI). Methods and results We enrolled 441 patients with heart failure undergoing elective PCI from 2012 to 2018. Pre‐procedural estimated PVS by the Duarte's formula (Duarte‐ePVS) and Kaplan–Hakim formula (KH‐ePVS) were calculated for all patients. CIN was defined as an absolute serum creatinine (SCr) increase ≥0.5 mg/dL or a relative increase ≥25% compared with the baseline value within 48 h of contrast medium exposure. We assessed the association between PVS and CIN in patients with heart failure undergoing elective PCI. In 441 patients, 28 (6.3%) patients developed CIN. The median Duarte‐ePVS was 4.44 (3.87, 5.13) and the median KH‐ePVS was −0.03 (−0.09, 0.05). The best cutoff values for Duarte‐ePVS and KH‐ePVS to predict CIN were 4.64 (with 78.6% sensitivity and 61.7% specificity) and 0.04 (with 64.5% sensitivity and 75.5% specificity), respectively. After adjusting for potential confounding variables, KH‐ePVS > 0.04 [odds ratio (OR) 2.685, 95% confidence interval (CI) 1.012–7.123, P = 0.047] remained significantly associated with CIN whereas Duarte‐ePVS was not. Conclusions Pre‐procedural KH‐ePVS is an independent risk factor for CIN in patients with heart failure undergoing elective PCI. The best cutoff point of KH‐ePVS for predicting CIN was 0.04.

The aims of the present study is to evaluate the roles of collagen I and III in the hip capsule in the postoperative clinical function of patients with developmental dysplasia of the hip (DDH). Hip capsules from 155 hips of 120 patients were collected during surgery. The patients were divided into three groups according to age: I: 2–3.5 years; II: 3.5–5 years; and III: 5–6 years. Patient clinical function and radiographic outcomes were evaluated with the McKay scores and Severin classification. The expression of collagen I and III was detected through immunohistochemistry and quantitative reverse transcription polymerase chain reaction (RT-PCR) and analyzed according to age, sex, degree of dislocation and McKay classification. All patients received open reduction and pelvic osteotomy and/or femoral shortening osteotomy and achieved good results on the basis of postoperative X-ray imaging. The average follow-up time was 3.4 years (range 2–4.3 years). There were no changes in the expression of collagen III in the different groups. The expression of collagen I according to age and sex was not significantly different. Lower expression of collagen I was observed in DDH patients with a higher degree of dislocation according to the Tonnis grade. The highest expression of collagen I was detected in the group with poor clinical function according to the McKay classification. Collagen I is correlated with the degree of dislocation and is a risk factor for poor clinical function in DDH patients. Collagen I is correlated with the degree of hip dislocation and poor clinical function in DDH patients.

Wnt/β-catenin signaling has been well established as a potent inhibitor of adipogenesis. Here, we identified a population of adipocytes that exhibit persistent activity of Wnt/β-catenin signaling, as revealed by the Tcf/Lef-GFP reporter allele, in embryonic and adult mouse fat depots, named as Wnt+ adipocytes. We showed that this β-catenin-mediated signaling activation in these cells is Wnt ligand- and receptor-independent but relies on AKT/mTOR pathway and is essential for cell survival. Such adipocytes are distinct from classical ones in transcriptomic and genomic signatures and can be induced from various sources of mesenchymal stromal cells including human cells. Genetic lineage-tracing and targeted cell ablation studies revealed that these adipocytes convert into beige adipocytes directly and are also required for beige fat recruitment under thermal challenge, demonstrating both cell autonomous and non-cell autonomous roles in adaptive thermogenesis. Furthermore, mice bearing targeted ablation of these adipocytes exhibited glucose intolerance, while mice receiving exogenously supplied such cells manifested enhanced glucose utilization. Our studies uncover a unique adipocyte population in regulating beiging in adipose tissues and systemic glucose homeostasis.

Abstract With the increasing demand for antimicrobial agents and the spread of antibiotic resistance in pathogens, the exploitation of plant oils to partly replace antibiotic emerges as an important source of fine chemicals, functional food utility and pharmaceutical industries. This work introduces a novel catalytic method of plant oils hydroxylation by Fe(III) citrate monohydrate (Fe3+-cit.)/Na2S2O8 catalyst. Methyl (9Z,12Z)-octadecadienoate (ML) was selected as an example of vegetable oils hydroxylation to its hydroxy-conjugated derivatives (CHML) in the presence of a new complex of Fe(II)-species. Methyl 9,12-di-hydroxyoctadecanoate 1, methyl-9-hydroxyoctadecanoate 2 and methyl (10E,12E)-octadecanoate 3 mixtures is produced under optimized condition with oxygen balloon. The specific hydroxylation activity was lower in the case of using Na2S2O8 alone as a catalyst. A chemical reaction has shown the main process converted of plantoils hydroxylation and (+ 16 Da) of OH- attached at the methyl linoleate (ML-OH). HPLC and MALDI-ToF-mass spectrometry were employed for determining the obtained products. It was found that adding oxidizing agents (Na2S2O8) to Fe3+ in the MeCN mixture with H2O would generate the new complex of Fe(II)-species, which improves the C-H activation. Hence, the present study demonstrated a new functional method for better usage of vegetable oils.Producing conjugated hydroxy-fatty acids/esters with better antipathogenic properties. CHML used in food industry, It has a potential pathway to food safety and packaging process with good advantages, fundamental to microbial resistance. Lastly, our findings showed that biological monitoring of CHML-minimum inhibitory concentration (MIC) inhibited growth of various gram-positive and gram-negative bacteria in vitro study. The produced CHML profiles were comparable to the corresponding to previousstudies and showed improved the inhibition efficiency over the respective kanamycin derivatives.

Soil biodiversity drives soil-based ecosystem services and is an important indicator of soil health. To understand the responses of important soil biological indicators to different farmland use contexts, 72 fields in three agricultural regions of China were used as research objects. The distribution characteristics and the factors influencing six indicators (carbon and nitrogen contents of soil microbial biomass (MBC, MBN, respectively), soil respiration (SR), soil catalase activity (CAT), soil acid phosphomonoesterase activity (APA), and soil earthworms) were investigated using field monitoring and indoor analysis. The MBC, SR, CAT, and APA indicators showed significant differences among the regions (p < 0.05). Correlation and redundancy analyses indicated that the important factors affecting MBC, MBN, and soil respiration were cation exchange capacity, total N, organic matter, hydrolytic N, and soil bulk density, whereas the important factors affecting APA and earthworms were total phosphorus, available phosphorus, and available potassium. None of these factors had a significant effect on CAT. Climatic conditions, soil types, and farmland practices all have complex impacts on soil biodiversity. The results showed that attention should be paid to improving the physical conditions of the soil and to increasing soil fertility levels when establishing sustainable farm management patterns.

Background: Balloon pulmonary angioplasty (BPA)-related complications are not uncommon and could contribute to perioperative mortality. However, there is a lack of a prediction model for BPA-related complications. Methods: Data from consecutive patients diagnosed with chronic thromboembolic pulmonary hypertension (CTEPH) who underwent BPA were retrospectively analyzed. The primary outcome was BPA-related complications. The secondary outcomes were mortality and hemodynamics after BPA. Results: A total of 207 patients with 614 BPA sessions were included. Complications occurred during 63 sessions (10.26%) in 49 patients. Hemoptysis or hemosputum (6.51%) was the most common complication, whereas pulmonary reperfusion edema was rare (0.49%). Multivariable logistic regression identified that disease duration, mean pulmonary arterial pressure (mPAP) and the proportion of occlusion lesions were correlated with BPA complications. A nomogram was constructed accordingly, which had the highest area under curve (0.703) and was superior to previously reported predictors [nomogram vs. mPAP, net reclassification index (95% confidence interval (CI)), 0.215 (0.002, 0.427), p = 0.047; integrated discrimination index (95% CI), 0.059 (0.010, 0.109), p = 0.018]. The nomogram was found to be accurate based on validation and calibration (slope 0.978, Bier score 0.163). After adjusting for the number of BPA sessions in multivariable linear regression, the occurrence of complications was not associated with hemodynamic improvement after BPA. The 3-year survival was also comparable between patients with and without complications (98.0% vs. 94.8%, log-rank p = 0.503). Conclusions: The nomogram, comprising mPAP, the proportion of occlusion lesions and disease duration, could better predict BPA-related complications than previously reported single parameters. Distinctively, the occurrence of complications did not impair the beneficial impact of BPA on hemodynamics and survival. The occurrence of complications should not discourage patients from continuing BPA sessions.

In this article, the catalysts of hydrotalcite-derived Ni1.5Co0.5AlO nanosheet-supported highly dispersed Pt nanoparticles (Ptn/Ni1.5Co0.5AlO, where n% is the weigh percentage of the Pt element in the catalysts) were elaborately fabricated by the gas-bubble-assisted membrane--reduction method. The specific porous structure formed by the stack of hydrotalcite-derived Ni1.5Co0.5AlO nanosheets can increase the transfer mass efficiency of the reactants (O2, NO, and soot) and the strong Pt–Ni1.5Co0.5AlO interaction can weaken the Ni/Co-O bond for promoting the mobility of lattice oxygen and the formation of surface-oxygen vacancies. The Ptn/Ni1.5Co0.5AlO catalysts exhibited excellent catalytic activity and stability during diesel soot combustion under the loose contact mode between soot particles and catalysts. Among all the catalysts, the Pt2/Ni1.5Co0.5AlO catalyst showed the highest catalytic activities for soot combustion (T50 = 350 °C, TOF = 6.63 × 10−3 s−1). Based on the characterization results, the catalytic mechanism for soot combustion is proposed: the synergistic effect of Pt and dual Ni/Co cations in the Pt/Ni1.5Co0.5AlO catalysts can promote the vital step of catalyzing NO oxidation to NO2 in the NO-assisted soot oxidation mechanism. This insight into the synergistic effect of Pt and dual Ni/Co cations for soot combustion provides new strategies for reducing the amounts of noble metals in high-efficient catalysts.

Background: Contrast-associated acute kidney injury (CA-AKI) is responsible for a substantial proportion of the observed mortality that occurs after percutaneous coronary intervention (PCI), particularly in elderly patients. However, there has been significant and debate over whether the optimal definition of CA-AKI persists over prolonged periods due to variations in the prevalence and effects on prognosis. In this study, we aimed to identify whether different definitions of CA-AKI exert differential impacts on long-term mortality when compared between elderly and non-elderly patients receiving elective PCI.Methods: We prospectively investigated 5,587 consenting patients undergoing elective PCI between January 2012 and December 2018. We considered two classical definitions of CA-AKI from the European Society of Urogenital Radiology (ESUR) and the Acute Kidney Injury Network (AKIN). Multivariable Cox regression analysis was used to investigate the association between CA-AKI and long-term mortality. We also performed interaction and stratified analyses according to age (≤75 or >75 years).Results: The incidence of CA-AKI according to the ESUR and AKIN definitions was 18.7 and 6.1%, respectively. After a median follow-up of 2.1 years, multivariable Cox regression analysis indicated that CA-AKI according to the AKIN definition was a risk factor for long-term mortality in the overall population [hazard ratio (HR) = 2.20; 95% confidential interval (CI): 1.51–3.22; p < 0.001]; however, this was not the case for the ESUR definition (HR = 1.27; 95% CI: 0.92–1.76; p = 0.153). Further interaction analysis identified a significant interaction between age and the ESUR definition (p = 0.040). Stratified analyses also found an association between the ESUR definition and long-term mortality in patients >75 years of age (p = 0.011), but not in patients ≤75 years of age (p = 0.657).Conclusion: As a stringent definition of CA-AKI, the AKIN definition was significantly associated with long-term mortality in both non-elderly and elderly patients. However, in elderly patients, the more lenient definition provided by the ESUR was also significantly correlated with long-term mortality, which could sensitively identify high-risk elderly patients and may provide a better alternative.

RNA is a unique biomolecule that is involved in a variety of fundamental biological functions, all of which depend solely on its structure and dynamics. Since the experimental determination of crystal RNA structures is laborious, computational 3D structure prediction methods are experiencing an ongoing and thriving development. Such methods can lead to many models; thus, it is necessary to build comparisons and extract common structural motifs for further medical or biological studies. Here, we introduce a computational pipeline dedicated to reference-free high-throughput comparative analysis of 3D RNA structures. We show its application in the RNA-Puzzles challenge, in which five participating groups attempted to predict the three-dimensional structures of 5′- and 3′-untranslated regions (UTRs) of the SARS-CoV-2 genome. We report the results of this puzzle and discuss the structural motifs obtained from the analysis. All simulated models and tools incorporated into the pipeline are open to scientific and academic use.

Abstract Background Hertwig’s epithelial root sheath (HERS) is important in guiding tooth root formation by differentiating into cementoblasts through epithelial–mesenchymal transition (EMT) and inducing odontoblastic differentiation of dental papilla through epithelial–mesenchymal interaction (EMI) during the tooth root development. Thus, HERS cells are critical for cementum and dentin formation and might be a potential cell source to achieve tooth root regeneration. However, limited availability and lifespan of primary HERS cells may represent an obstacle for biological investigation and therapeutic use of tooth tissue engineering. Therefore, we constructed, characterized, and tested the functionality of immortalized cell lines in order to produce a more readily available alternative to HERS cells. Methods Primary HERS cells were immortalized via infection with lentivirus vector containing the gene encoding simian virus 40 Large T Antigen (SV40LT). Immortalized HERS cell subclones were isolated using a limiting dilution method, and subclones named HERS-H1 and HERS-C2 cells were isolated. The characteristics of HERS-H1 and HERS-C2 cells, including cell proliferation, ability of epithelial–mesenchymal transformation and epithelial–mesenchymal interaction, were determined by CCK-8 assay, immunofluorescence staining, and real-time PCR. The cell differentiation into cementoblast-like cells or periodontal fibroblast-like cells was confirmed in vivo. And the inductive influence of the cell lines on dental papilla cells (DPCs) was also confirmed in vivo. Results HERS-H1 and HERS-C2 cells share some common features with primary HERS cells such as epithelial-like morphology, positive expression of CK14, E-Cadherin, and Vimentin, and undergoing EMT in response to TGF-beta. HERS-C2 cells showed the EMT characteristics and could differentiate into cementum-forming cells in vitro and generate cementum-like tissue in vivo. HERS-H1 could induce the differentiation of DPCs into odontoblasts in vitro and generation of dentin-like tissue in vivo. Conclusions We successfully isolated and characterized novel cell lines representing two key features of HERS cells during the tooth root development and which were useful substitutes for primary HERS cells, thereby providing a biologically relevant, unlimited cell source for studies on cell biology, developmental biology, and tooth root regeneration.

Vitamin D plays a crucial role in regulation of the immune response. However, treatment of autoimmune diseases with 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] doses sufficient to be effective is prohibitive due to its calcemic and toxic effects. We use the collagen-induced arthritis (CIA) model to analyze the efficacy of the noncalcemic analog of vitamin D, 20S-hydroxyvitamin D3 [20S(OH)D3], as well as 1,25(OH)2D3, to attenuate arthritis and explore a potential mechanism of action. Mice fed a diet deficient in vitamin D developed a more severe arthritis characterized by enhanced secretion of T cell inflammatory cytokines, compared to mice fed a normal diet. The T cell inflammatory cytokines were effectively suppressed, however, by culture of the cells with 20S(OH)D3. Interestingly, one of the consequences of culture with 1,25(OH)2D3 or 20S(OH)D3, was upregulation of the natural inhibitory receptor leukocyte associated immunoglobulin-like receptor-1 (LAIR-1 or CD305). Polyclonal antibodies which activate LAIR-1 were also capable of attenuating arthritis. Moreover, oral therapy with active forms of vitamin D suppressed arthritis in LAIR-1 sufficient DR1 mice, but were ineffective in LAIR-1−/− deficient mice. Taken together, these data show that the effect of vitamin D on inflammation is at least, in part, mediated by LAIR-1 and that non-calcemic 20S(OH)D3 may be a promising therapeutic agent for the treatment of autoimmune diseases such as Rheumatoid Arthritis.

We previously demonstrated that the non-calcemic pregnacalciferol (pD) analog 17,20S (OH)2pD suppressed TGF-β1-induced type I collagen production in cultured normal human dermal fibroblasts. In the present studies, we examined fibroblasts cultured from the lesional skin of patients with systemic sclerosis (scleroderma (SSc)) and assessed the effects of 17,20S(OH)2pD on fibrosis-related mediators. Dermal fibroblast lines were established from skin biopsies from patients with SSc and healthy controls. Fibroblasts were cultured with either 17,20S(OH)2pD or 1,25(OH)2D3 (positive control) with/without TGF-β1 stimulation and extracted for protein and/or mRNA for collagen synthesis and mediators of fibrosis (MMP-1, TIMP-1, PAI-1, BMP-7, PGES, GLI1, and GLI2). 1 7,20S(OH)2pD (similar to 1,25(OH)2D3) significantly suppressed net total collagen production in TGF-β1-stimulated normal donor fibroblast cultures and in cultures of SSc dermal fibroblasts. 17,20S(OH)2pD (similar to 1,25(OH)2D3) also increased MMP-1, BMP-7, and PGES and decreased TIMP-1 and PAI1 expression in SSc fibroblasts. Although 17,20S(OH)2pD had no effect on Gli1 or Gli2 in SSc fibroblasts, it increased Gli2 expression when cultured with TGF-β1 in normal fibroblasts. These studies demonstrated that 17,20S(OH)2pD modulates mediators of fibrosis to favor the reduction of fibrosis and may offer new noncalcemic secosteroidal therapeutic approaches for treating SSc and fibrosis.

To implement the balance system of cultivated land in occupation and supplement and to adhere to the principle of “supplement the occupied cultivated land of high quality with the one bearing same quality”, in the thesis, a field experiment was conducted to study the effects of woody peat on soil physical, chemical, and biological properties of the plough layer and its crop yield. Furthermore, the correlation between soil indexes and crop yield under the best fertilization mode through the addition of the natural material of woody peat instead of lengthy cultivation of the plough layer to rapidly construct a high-quality plough layer and solve the practical problem that the natural endowment of newly reclaimed cultivated land is far less than the occupied high-quality cultivated land was explored. The land remediation project of Fuping County, Hebei Province, was taken as the experimental area, and the five most representative and effective datasets were selected and studied. The results demonstrated that the addition of woody peat and rotten straw could reduce soil particle size and bulk density and alleviate soil viscosity and acidification. An increase in soil organic matter, soil microbial biomass carbon (MBC), alkali-hydrolyzable nitrogen, available phosphorus, and available potassium and a decrease in the heavy metal content were also observed. The results indicated that the application of woody peat achieved the expected effect of the rapid construction of a high-quality plough layer. The best mode of fertilization was A2, which provided a good reference for the rapid construction of a high-quality plough layer in the future. The analysis of the correlation between soil indexes and crop yield illustrated that the organic matter content, soil available nutrients, and crop yield had a significant positive correlation; the organic matter content and soil available nutrients showed the same tendency, which suggests that soil organic matter content and soil fertility level are closely related and that soil fertility plays a decisive role in crop yield under the same external conditions. Woody peat exerted an eminent influence on the organic matter content and soil available nutrients to determine the change in crop yield, which provides a reliable basis for future research on land improvement projects to increase crop yield.

Cultivated Land Balance Policy (CLBP) has led to the “better land occupied and worse land supplemented” program. At the same time, the current field-scale cultivated land quality (CLQ) evaluation cannot meet the work requirements of the CLBP. To this end, this study selected 24 newly added farmland in Fuping County and performed eight different high quality farming layer construction experiments to improve the CLQ. A new comprehensive model was constructed on a field scale to evaluate the CLQ using different tests from multi-dimensional perspectives of soil fertility, engineering, environment, and ecology, and to determine the best test mode. The results showed that after the test, around 62% of the cultivated land improved by one level, and the average cultivated land quality level and quality index of the test area increased by 0.63 and 30.63, respectively. The treatment of “woody peat + rotten crop straw + biostimulation regulator II + conventional fertilization” had the best effect on the improvement of organic matter, soil aggregates, and soil microbial activity, and was the best treatment method. In general, application of soil amendments, such as woody peat when constructing high quality farmland, could quickly improve CLQ, and field-scale CLQ evaluation model constructed from a multi-dimensional perspective could accurately assess the true quality of farmland and allow managers to improve and manage arable land resources under CLBP.

Systemic sclerosis (SSc; scleroderma) is a chronic fibrotic disease involving TGF-β1. Low serum vitamin D (vit D) correlates with the degree of fibrosis and expression of TGF-β1. This study was designed to determine whether the noncalcemic vit D analog, 17,20S(OH)2pD, suppresses fibrosis and mediators of the TGF-β1 pathway in the bleomycin (BLM) model of fibrosis. Fibrosis was induced into the skin of female C57BL/6 mice by repeated injections of BLM (50 μg/100 μL) subcutaneously. Mice received daily oral gavage with either vehicle (propylene glycol) or 17,20S(OH)2pD using 5, 15, or 30 μg/kg for 21 days. The injected skin was biopsied; analyzed histologically; examined for total collagen by Sircol; and examined for mRNA expression of MMP-13, BMP-7, MCP-1, Gli1, and Gli2 by TR-PCR. Spleen was analyzed for lymphocytes using flow cytometry. Serum was analyzed for cytokines using a multiplexed ELISA. Results showed that all three doses of 17,20S(OH)2pD suppressed net total collagen production, dermal thickness, and total collagen content in the BLM fibrosis model. 17,20S(OH)2pD also increased MMP-13 expression, decreased MCP-1 and Gli-2 expression in vivo, and suppressed serum levels of IL-13, TNF-α, IL-6, IL-10, IL-17, and IL-12p70. In summary, 17,20S(OH)2pD modulates the mediators of fibrosis in vivo and suppresses total collagen production and dermal thickness. This antifibrotic property of 17,20S(OH)2pD offers new therapeutic approaches for fibrotic disorders.

Vitamin D, a fat-soluble prohormone, is endogenously synthesized in response to sunlight or taken from dietary supplements. Since vitamin D receptors are present in most tissues and cells in the body, the mounting understanding of the role of vitamin D in humans indicates that it does not only play an important role in the musculoskeletal system, but has beneficial effects elsewhere as well. This review summarizes the metabolism of vitamin D, the research regarding the possible risk factors leading to vitamin D deficiency, and the relationships between vitamin D deficiency and numerous illnesses, including rickets, osteoporosis and osteomalacia, muscle weakness and falls, autoimmune disorders, infectious diseases, cardiovascular diseases (CVDs), cancers, and neurological disorders. The system-wide effects of vitamin D and the mechanisms of the diseases are also discussed. Although accumulating evidence supports associations of vitamin D deficiency with physical and mental disorders and beneficial effects of vitamin D with health maintenance and disease prevention, there continue to be controversies over the beneficial effects of vitamin D. Thus, more well-designed and statistically powered trials are required to enable the assessment of vitamin D’s role in optimizing health and preventing disease.