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Abstract The recently synthesized monolayer MoSi2N4 (Science 2020, 369, 367) exhibits exceptional environmental stability, a moderate band gap, and excellent mechanical properties, presenting exciting opportunities for the exploration of two-dimensional (2D) MX2Z4 materials. However, the low carrier mobility of α-phase MoSi2N4 significantly limits its potential applications in field-effect transistor (FET) devices. In this study, we systematically investigate the structural stability, elastic properties, and carrier mobility of a novel family of β-phase MX2N4 (M = Mo, W; X = Si, Ge) monolayers through first-principles calculations. Our findings reveal that these β-phase MX2N4 monolayers demonstrate remarkable dynamic, thermal, and mechanical stability. Specifically, we identify the MoSi2N4, MoGe2N4, WSi2N4, and WGe2N4 monolayers as semiconductors with band gaps of 2.70 eV, 1.57 eV, 3.12 eV, and 1.93 eV, respectively, as calculated using the HSE06 functional. Moreover, the MX2N4 monolayers exhibit significant elastic anisotropy, characterized by high ideal tensile strengths and a critical tensile strain exceeding 25%. Notably, the WGe2N4 monolayer displays exceptional anisotropic in-plane charge transport, achieving mobility levels of up to 104 cm2V− 1S− 1, surpassing those of the α-phase MX2N4 monolayers. These novel ternary monolayer structures have the potential to broaden the 2D MX2Z4 material family and emerge as promising candidates for applications in field-effect transistors.

With the development of China's economic level and improving people's living standards, the state's supervision of food health and safety has increased. Consumer demand for many people has gradually changed from being satiated to eating well, and high-quality, environmentally friendly, and healthy aquatic products have become increasingly popular with consumers. However, intensive and high-density aquaculture causes the deterioration of water environmental conditions, the increase of anti-nutrient factors and nutritional imbalance caused by the replacement of animal protein with plant protein in feed, and changes in the growth, immunity, and digestive ability of aquatic animals caused by changes in feed nutrients, traditional processing methods, and transportation stress. The above situations encountered in aquaculture have a common impact on aquatic animals and inevitably cause a reduction in the muscle quality of aquatic animals. Therefore, improving the muscle quality of aquatic animals and the quality of aquatic products is an urgent problem with significant research value and potential.To improve aquatic quality, first, it is necessary to first identify the indicators of muscle quality in aquatic animals to improve aquatic quality. However, there is still a lack of a systematic muscle quality evaluation index system in the current aquaculture research. Therefore, this study reviewed the evaluation indices of muscle quality, including meat content, muscle nutrient composition, muscle fiber structure, muscle texture characteristics, and muscle physicochemical indices, to provide a reference for establishing scientific muscle quality evaluation indices. In addition, factors affecting muscle quality must be considered in studies aimed at improving the muscle quality of aquatic animals. Only by understanding the factors affecting muscle quality in aquatic animals can the key factors regulating muscle quality and their mechanisms be studied more comprehensively and scientifically. This study reviewed the factors affecting the muscle quality of aquatic animals, including feed nutrients, feed additives, and the culturing environment, and found that nutrients are key factors in improving the muscle quality of aquatic animals.Protein is an important nutrient, the main component of muscle, and an important indicator of muscle quality. Amino acids are the basic units of proteins and have a vital impact on muscle quality and flavor. Therefore, it is important to study the effects and mechanisms of action of amino acids on muscle quality in aquatic animals. Therefore, the effects of dietary amino acids on the muscle quality of aquatic animals were reviewed in this study, including the effects of amino acids on muscle nutrients, flavor, texture indices, and physical and chemical properties of aquatic animals. Furthermore, the effects of amino acids on muscle quality, including the promotion of protein synthesis, regulation of fat deposition, enhancement of antioxidant activity, and maintenance of intestinal health, were reviewed.In summary, this study summarized the influence of amino acids on the muscle quality of aquatic animals and its mechanism from the aspects of muscle quality evaluation indices, factors affecting meat quality, and the influence of amino acids on muscle quality, providing a reference for further research on the regulation of muscle quality by amino acids and the improvement of feed nutrients on the meat quality of aquatic animals.

Abstract The potential of adverse events (AEs) after thoracic endovascular aortic repair (TEVAR) in patients with type B aortic dissection (TBAD) has been reported. To avoid the occurrence of AEs, it is important to recognize high-risk population for prevention in advance. The data of 261 patients with TBAD who received TEVAR between June 2017 and June 2021 at our medical center were retrospectively reviewed. After the implementation of exclusion criteria, 172 patients were finally included, and after 2.8 years (range from 1 day to 5.8 years) of follow up, they were divided into AEs (n = 41) and non-AEs (n = 131) groups. We identified the predictors of AEs, and a prediction model was constructed to calculate the specific risk of postoperative AEs at 1, 2, and 3 years, and to stratify patients into high-risk (n = 78) and low-risk (n = 94) group. The prediction model included seven predictors: Age > 75 years, Lower extremity malperfusion (LEM), NT-proBNP > 330 pg/ml, None distal tear, the ratio between the diameter of the ascending aorta and descending aorta (A/D ratio) > 1.2, the ratio of the area of the false lumen to the total aorta (FL ratio) > 64%, and acute TEVAR, which exhibited excellent predictive accuracy performance and discriminatory ability with C statistic of 82.3% (95% CI 77.3–89.2%). The prediction model was contributed to identify high-risk patients of postoperative AEs, which may serve to achievement of personalized treatment and follow-up plans for patients.

Abstract Background Hypertension is a main contributing factor of cardiovascular diseases; deregulated circular RNAs are involved in the pathogenesis of pulmonary arterial hypertension (PAH). Herein, we evaluated the function and mechanism of circST6GAL1 in PAH process. Methods Human pulmonary artery smooth muscle cells (HPASMCs) were cultured in hypoxic environment for functional analysis. The cell counting kit‐8, 5‐ethynyl‐2′‐deoxyuridine, wound healing, and flow cytometry assays were used to investigate cell proliferation, migration, and apoptosis. qRT‐PCR and Western blotting analyses were used for level measurement of genes and proteins. The binding between miR‐509‐5p and circST6GAL1 or multiple C2 and transmembrane domain containing 2 (MCTP2) was analyzed by dual‐luciferase reporter, RNA immunoprecipitation, and pull‐down assays. The monocrotaline (MCT)‐induced PAH mouse models were established for in vivo assay. Results CircST6GAL1 was highly expressed in PAH patients and hypoxia‐induced HPASMCs. Functionally, circST6GAL1 deficiency reversed hypoxia‐induced proliferation and migration, as well as apoptosis arrest in HPASMCs. Mechanistically, circST6GAL1 directly targeted miR‐509‐5p, and MCTP2 was a target of miR‐509‐5p. Rescue assays showed that the regulatory effects of circST6GAL1 deficiency on hypoxia‐induced HPASMCs were abolished. Moreover, forced expression of miR‐509‐5p suppressed HPASMC proliferation and migration and induced cell apoptosis under hypoxia stimulation, while these effects were abolished by MCTP2 overexpression. Moreover, circST6GAL1 silencing improved MCT‐induced pulmonary vascular remodeling and PAH. Conclusion CircST6GAL1 deficiency reversed hypoxia‐induced proliferation and migration, as well as apoptosis arrest in HPASMCs, and alleviated pulmonary vascular remodeling in MCT‐induced PAH mouse models through the miR‐509‐5p/MCTP2 axis, indicating a potential therapeutic target for PAH.

BackgroundAccurate and rapid discrimination between benign and malignant ovarian masses is crucial for optimal patient management. This study aimed to establish an ultrasound image-based nomogram combining clinical, radiomics, and deep transfer learning features to automatically classify the ovarian masses into low risk and intermediate-high risk of malignancy lesions according to the Ovarian- Adnexal Reporting and Data System (O-RADS).MethodsThe ultrasound images of 1,080 patients with 1,080 ovarian masses were included. The training cohort consisting of 683 patients was collected at the South China Hospital of Shenzhen University, and the test cohort consisting of 397 patients was collected at the Shenzhen University General Hospital. The workflow included image segmentation, feature extraction, feature selection, and model construction.ResultsThe pre-trained Resnet-101 model achieved the best performance. Among the different mono-modal features and fusion feature models, nomogram achieved the highest level of diagnostic performance (AUC: 0.930, accuracy: 84.9%, sensitivity: 93.5%, specificity: 81.7%, PPV: 65.4%, NPV: 97.1%, precision: 65.4%). The diagnostic indices of the nomogram were higher than those of junior radiologists, and the diagnostic indices of junior radiologists significantly improved with the assistance of the model. The calibration curves showed good agreement between the prediction of nomogram and actual classification of ovarian masses. The decision curve analysis showed that the nomogram was clinically useful.ConclusionThis model exhibited a satisfactory diagnostic performance compared to junior radiologists. It has the potential to improve the level of expertise of junior radiologists and provide a fast and effective method for ovarian cancer screening.

BackgroundAccurately differentiating between ovarian endometrioma and ovarian dermoid cyst is of clinical significance. However, the ultrasound appearance of these two diseases is variable, occasionally causing confusion and overlap with each other. This study aimed to develop a diagnostic classification model based on ultrasound radiomics to intelligently distinguish and diagnose the two diseases.MethodsWe collected ovarian ultrasound images from participants diagnosed as patients with ovarian endometrioma or ovarian dermoid cyst. Feature extraction and selection were performed using the Mann-Whitney U-test, Spearman correlation analysis, and the least absolute shrinkage and selection operator (LASSO) regression. We then input the final features into the machine learning classifiers for model construction. A nomogram was established by combining the radiomic signature and clinical signature.ResultsA total of 407 participants with 407 lesions were included and categorized into the ovarian endometriomas group (n = 200) and the dermoid cyst group (n = 207). In the test cohort, Logistic Regression (LR) achieved the highest area under curve (AUC) value (0.981, 95% CI: 0.963−1.000), the highest accuracy (94.8%), and the highest sensitivity (95.5%), while LightGBM achieved the highest specificity (97.1%). A nomogram incorporating both clinical features and radiomic features achieved the highest level of performance (AUC: 0.987, 95% CI: 0.967−1.000, accuracy: 95.1%, sensitivity: 88.0%, specificity: 100.0%, PPV: 100.0%, NPV: 88.0%, precision: 93.6%). No statistical difference in diagnostic performance was observed between the radiomic model and the nomogram (P > 0.05). The diagnostic indexes of radiomic model were comparable to that of senior radiologists and superior to that of junior radiologist. The diagnostic performance of junior radiologists significantly improved with the assistance of the model.ConclusionThis ultrasound radiomics-based model demonstrated superior diagnostic performance compared to those of junior radiologists and comparable diagnostic performance to those of senior radiologists, and it has the potential to enhance the diagnostic performance of junior radiologists.

A suitable feed size has a positive effect on animal feeding. For aquatic larvae, the correct feed size is very important for their growth. This experiment analyzed and compared the effect of different particle sizes of feed for larval stages on the growth performance, whole body composition, and muscle amino acid and fatty acid composition of crayfish. Five larval crayfish diets of different particle sizes, namely < 0.40 mm (Group A, control group), 0.40–0.50 mm (Group B), 0.71–0.85 mm (Group C), 0.90–1.00 mm (Group D) and 1.5 mm (Group E), were fed to 2000 crayfish (initial weight 0.0786 ± 0.0031 g) for 100 d. The results showed that as the particle size increased, final weight, weight gain (WG, p = 0.001) and specific growth rate (SGR, p = 0.000) of the crayfish tended to increase and then leveled off, with the control group being the lowest. The feed conversion ratio (FCR, p = 0.000) showed a decreasing and then equalizing trend with increasing particle size, but there was no significant difference between the groups except the control group. Broken-line regression analysis showed that the critical values for the appropriate particle feed size for crayfish larvae were 0.55 mm and 0.537 mm using SGR and FCR as indicators. Groups B, C and D had the highest crude protein content and were significantly higher than the control group (p = 0.001). Group E had the highest umami amino acid (UAA) and was significantly higher than the control group (p = 0.026). The content of isoleucine (Ile, p = 0.038) and phenylalanine (Phe, p = 0.038) was highest in group C and significantly higher than in the control group. Through principal component analysis, groups C and D were shown to contain leucine (Leu), glutamic (Glu), methionine (Met), valine (Val), histidine (His), Phe, and Ile levels significantly induced. The content of linoleic acid (C18:2n6, p = 0.000), linolenic acid (C18:3n3, p = 0.000), saturated fatty acid (SFA, p = 0.000), monounsaturated fatty acid (MUFA, p = 0.001), polyunsaturated fatty acid (PUFA, p = 0.000) and n-6 PUFA (p = 0.000) in group C was the highest and significantly higher than the control group. Principal component analysis showed that group C significantly induced the levels of C18:2n6, C18:3n3, DHA, EPA, n-3 PUFA and n-6 PUFA in muscle. Therefore, our results suggest that appropriate feed particle size can improve the growth performance and nutrient composition of crayfish. Based on the broken-line regression analysis of SGR and FCR, the critical values of optimal particle size for crayfish are 0.55 mm and 0.537 mm, and when the particle size exceeds these critical values (not more than 1.5 mm commercial feed), growth performance and FCR of the crayfish are no longer changed. Nevertheless, group C has high protein and low lipid content, as well as better nutrition with amino acids and fatty acids. Overall, combined with growth performance and nutrient composition, it is recommended that the particle size of the diet at the larval stage for crayfish is between 0.71 and 0.85 mm.

BackgroundAlzheimer's disease (AD) is a common elderly disorder characterized by cognitive decline. Endoplasmic reticulum (ER) stress has been implicated in various neurodegenerative diseases, including AD. Stem cell factor (SCF) performs its biological functions by binding to and activating receptor tyrosine kinase c-Kit. We aimed to investigate the effects of SCF/c-Kit and JAK2/STAT3 on ER stress and apoptosis in AD.MethodsThe study employed L-glutamic acid (L-Glu)-treated HT22 cells as sporadic AD cell model and APP/PS1 mice as an animal model of familiar AD. SCF, c-Kit inhibitor ISCK03 or JAK2/STAT3 inhibitor WP1066 was treated to verify the effects of SCF/c-Kit and JAK2/STAT3 on ER stress and apoptosis of L-Glu-exposed HT22 cells. Cell viability was assessed by MTT. BrdU detected cell proliferation. Flow cytometry measured cell apoptosis. The expression levels of ER stress markers GRP78, PERK, CHOP, and apoptosis protein caspase3 were determined by western blot. The effect on the mRNA of ER stress markers GRP78, PERK, CHOP and apoptotic caspase3 were quantified by RT-qPCR in primary cultured hippocampal neurons from APP/PS1 transgenic mice.ResultsAdministration of SCF significantly augmented the activity and proliferation of hippocampal neuronal cells, protecting cells against L-Glu induced ER stress-associated apoptosis. Moreover, the addition of ISCK03 (c-Kit inhibitor) or WP1066 (JAK2/STAT3 inhibitor) reversed SCF effects on ER stress and apoptosis in vitro.ConclusionWe found that SCF inhibits L-Glu-induced ER stress-associated apoptosis via JAK2/STAT3 axis in HT22 hippocampal neuronal cells, as well as in primary hippocampal neurons from APP/PS1 mice, which provides valuable insights into the molecular mechanisms underlying the pathogenesis of AD and explores novel therapeutic targets for both sporadic and familial AD.

In order to study the muscle quality of different crustaceans, we aim to provide a comprehensive assessment of their muscle quality characteristics as a theoretical reference. In this work, seven major species of farmed and consumer crustaceans were selected, including crayfish (Procambarus clarkii), freshwater prawns (Macrobrachium rosenbergii), pacific white shrimp (Litopenaeus vannamei), black tiger shrimp (Penaeus monodon), kuruma prawns (Penaeus japonicus), river prawns (Macrobranchium nipponense), and Chinese shrimp (Penaeus chinensis). Their morphometric parameters, nutritional composition, textural properties, and physical and chemical indexes were comparatively analyzed. The results showed that the meat content (MC, about 14.78%) of crayfish was significantly lower than that of the other six species. By contrast, pacific white shrimp had the highest MC, although the MCs of black tiger shrimp, kuruma prawns, and Chinese shrimp are greater than 40%. All seven crustacean species were high in protein and low in fat, while pacific white shrimp had the highest crude protein, crude lipid, and crude ash content compared to the other crustaceans. The content of threonine (Thr) was the highest in crayfish. The content of methionine (Met) and lysine (Lys) was the highest in freshwater prawns. The content of isoleucine (Ile), leucine (Leu), and non–essential amino acid (NEAA) was the highest in pacific white shrimp. C18:2n-6 (linoleic acid, LA) was the highest in freshwater prawns and pacific white shrimp; C18:3n-3 (linolenic acid, LNA), C20:4n-6 (arachidonic acid, AA), unsaturated fatty acids (UFA), and monounsaturated fatty acids (MUFA) were all the highest in crayfish; and polyunsaturated fatty acids (PUFA) was the highest in freshwater prawns, but the content was not significantly different from crayfish, pacific white shrimp, black tiger shrimp, and Chinese shrimp. Pacific white shrimp had the highest values for hardness, cohesiveness, gumminess, and chewiness. The redness values of crayfish, black tiger shrimp, and Chinese shrimp were significantly higher than those of the other three species except kuruma prawns. Compared to other crustaceans, river prawns had the highest drip loss and cooking loss. Black tiger shrimp and Chinese shrimp had the lowest cooking loss rates. The research shows that the tail muscle of the seven species of crustaceans is rich in protein, essential amino acids, unsaturated fatty acids and low in fat, representing a high-quality protein. Among these crustaceans, the main essential amino acids and essential fatty acids in the tail muscle of pacific white shrimp, freshwater prawns, and crayfish are higher in content and better in nutritional value.

Abstract Here, a sucrose non‐fermenting‐1‐related protein kinase alpha subunit (TaSnRK1α‐1A) is identified as associated with cold stress through integration of genome‐wide association study, bulked segregant RNA sequencing, and virus‐induced gene silencing. It is confirmed that TaSnRK1α positively regulates cold tolerance by transgenes and ethyl methanesulfonate (EMS) mutants. A plastid‐lipid‐associated protein 6, chloroplastic‐like (TaPAP6L‐2B) strongly interacting with TaSnRK1α‐1A is screened. Molecular chaperone DJ‐1 family protein (TaDJ‐1‐7B) possibly bridged the interaction of TaSnRK1α‐1A and TaPAP6L‐2B. It is further revealed that TaSnRK1α‐1A phosphorylated TaPAP6L‐2B. Subsequently, a superior haplotype TaPAP6L‐2B30S/38S is identified and confirmed that both R30S and G38S are important phosphorylation sites that influence TaPAP6L‐2B in cold tolerance. Overexpression (OE) and EMS‐mutant lines verified TaPAP6L positively modulating cold tolerance. Furthermore, transcriptome sequencing revealed that TaPAP6L‐2B‐OE lines significantly increased jasmonic acid (JA) content, possibly by improving precursor α‐linolenic acid contributing to JA synthesis and by repressing JAR1 degrading JA. Exogenous JA significantly improved the cold tolerance of wheat plants. In summary, TaSnRK1α profoundly regulated cold stress, possibly through phosphorylating TaPAP6L to increase endogenous JA content of wheat plants.

Objective To investigate the distribution frequency and characteristics of Rh and Kell erythrocyte blood group antigens in Uygur population in Xinjiang, and to explore the molecular mechanism of K gene positive patients, so as to build a local rare blood group bank and improve the ability of clinical blood security. Methods From June 2018 to February 2020, blood samples of 4 000 unrelated Uygur healthy individuals from the Medical Examination Center of our hospital and other cooperative hospitals across the autonomous region were selected. Rh and Kell blood group antigens were detected using K/Rh antigen microcolumn gel cards. The exons of Kell gene were amplified by PCR and then subjected to electrophoresis and direct sequencing to investigate the molecular mechanism. Results In Xinjiang Uygur healthy population, 1) The RhD negative rate was 5.675% (227/4 000), including 5 phenotypes; RhD positive rate was 94.325% (3 773/4 000), including 9 phenotypes, which were in line with Hardy-Weinberg equilibrium distribution. The C/E antigen frequency in RhD negative and positive patients was 13.216%/4.185% vs 52.876%/25.788% (PC, g. 412A>G, exon 6, g. 133C>T, and g. 189T>C, respectively, two of which caused changes in amino acid sequence: alanine at position 193 to methionine (p.Ala193Met) and alanine 423 to valine (p.al423Val). The prediction of RNA secondary structure and protein conformation after mutation using relevant biological information software found that the mutation caused changes in RNA secondary structure, free energy, protein conformation and function. Conclusion The frequency of RhD antigen negative in Xinjiang Uygur population was higher than that in other ethnic groups, and the distribution of C/E antigen was different in D antigen negative/positive patients. The distribution of K antigen in Kell blood group system was higher than that in other ethnic groups (P

Cadmium (Cd) is a non-essential toxic metal in the body, which can cause harmful effects on the aquatic environment and aquatic organisms. In this study, the effects of acute Cd exposure on lipid metabolism disorder, oxidative stress and autophagy in abdominal muscles of Procambarus clarkii were investigated, as well the underlying molecular mechanisms were explored. P. clarkii were exposed to 0 (control), 1 and 5 mg Cd/l, respectively, for 5 days. We found that TG content, fas, hsl, and cpt1 gene expression levels, as well as the Srebp1 protein content in abdominal muscle decreased with the Cd concentrations increased, indicating that acute Cd exposure induced disorder of lipid metabolism in the abdominal muscle of P. clarkii. Further studies showed that acute Cd exposure provoked oxidative stress in the abdominal muscle of P. clarkii by increasing the accumulation of malondialdehyde (MDA) in the abdominal muscle. The oxidative stress of abdominal muscle induced by acute Cd exposure may be due to the reduction of catalases (CAT) and glutathione peroxidase (GPX) enzyme activities and Nrf2 protein content in the nucleus. The expression levels of autophagy-related genes (beclin1, atg101, atg13, atg3, atg4b, atg5, atg7, lc3a, lc3c atg9a) were also affected by acute Cd exposure, suggesting that acute Cd exposure also affected autophagy activity in abdominal muscle of P. clarkii. Our research indicates that waterborne acute Cd exposure can induce lipid metabolism disorder, and oxidative stress, and inhibit the expression of genes that trigger autophagy in the abdominal muscle of P. clarkii. These results may be useful for understanding the mechanism of Cd muscular toxicity in crustaceans.

Abstract Venous thromboembolism (VTE), clinically presenting as deep vein thrombosis (DVT) or pulmonary embolism (PE). Not all DVT patients carry the same risk of developing acute pulmonary embolism (APE). To develop and validate a prediction model to estimate risk of APE in DVT patients combined with past medical history, clinical symptoms, physical signs, and the sign of the electrocardiogram. We analyzed data from a retrospective cohort of patients who were diagnosed as symptomatic VTE from 2013 to 2018 (n = 1582). Among them, 122 patients were excluded. All enrolled patients confirmed by pulmonary angiography or computed tomography pulmonary angiography (CTPA) and compression venous ultrasonography. Using the LASSO and logistics regression, we derived a predictive model with 16 candidate variables to predict the risk of APE and completed internal validation. Overall, 52.9% patients had DVT + APE (773 vs 1460), 47.1% patients only had DVT (687 vs 1460). The APE risk prediction model included one pre-existing disease or condition (respiratory failure), one risk factors (infection), three symptoms (dyspnea, hemoptysis and syncope), five signs (skin cold clammy, tachycardia, diminished respiration, pulmonary rales and accentuation/splitting of P2), and six ECG indicators (SIQIIITIII, right axis deviation, left axis deviation, S1S2S3, T wave inversion and Q/q wave), of which all were positively associated with APE. The ROC curves of the model showed AUC of 0.79 (95% CI, 0.77–0.82) and 0.80 (95% CI, 0.76–0.84) in the training set and testing set. The model showed good predictive accuracy (calibration slope, 0.83 and Brier score, 0.18). Based on a retrospective single-center population study, we developed a novel prediction model to identify patients with different risks for APE in DVT patients, which may be useful for quickly estimating the probability of APE before obtaining definitive test results and speeding up emergency management processes.

Understanding the effects of dietary nutrients on physiological and biochemical parameters, especially the metabolism of nutrients during crayfish farming, can be useful for improving crayfish health and optimizing production in aquaculture. Therefore, we conducted an 8-week feeding study to investigate the effect of dietary carbohydrate-to-lipid (CHO: LIP) ratios on growth performance, hemolymph biochemical indices, intestinal digestion, hepatopancreas lipid, and carbohydrate metabolism of red swamp crayfish (Procambarus clarkii) (initial weight = 9.10 ± 0.15 g). Four isoenergetic and isonitrogenous diets (16.2 MJ kg−1 gross energy and 30.2% crude protein) were estimated to include different CHO:LIP ratios: 1.88 (22.5% CHO/11.9% LIP); 3.25 (29.3% CHO/9% LIP); 5.94 (36.2% CHO/6.1% LIP); and 13.60 (43.1% CHO/3.2% LIP). According to the results, the weight gain rate (WGR), final body weight, specific growth rate (SGR), intestinal amylase activity, abdominal muscle crude protein content, and protease activity significantly increased (P

Abstract Background At present, there is no generally accepted comprehensive prognostic risk prediction model for medically treated chronic thromboembolic pulmonary hypertension (CTEPH) patients. Methods Consecutive medically treated CTEPH patients were enrolled in a national multicenter prospective registry study from August 2009 to July 2018. A multivariable Cox proportional hazards model was utilized to derive the prognostic model, and a simplified risk score was created thereafter. Model performance was evaluated in terms of discrimination and calibration, and compared to the Swedish/COMPERA risk stratification method. Internal and external validation were conducted to validate the model performance. Results A total of 432 patients were enrolled. During a median follow-up time of 38.73 months (IQR: 20.79, 66.10), 94 patients (21.8%) died. The 1-, 3-, and 5-year survival estimates were 95.5%, 83.7%, and 70.9%, respectively. The final model included the following variables: the Swedish/COMPERA risk stratum (low-, intermediate- or high-risk stratum), pulmonary vascular resistance (PVR, ≤ or > 1600 dyn·s/cm5), total bilirubin (TBIL, ≤ or > 38 µmol/L) and chronic kidney disease (CKD, no or yes). Compared with the Swedish/COMPERA risk stratification method alone, both the derived model [C-index: 0.715; net reclassification improvement (NRI): 0.300; integrated discriminatory index (IDI): 0.095] and the risk score (C-index: 0.713; NRI: 0.300; IDI: 0.093) showed improved discriminatory power. The performance was validated in a validation cohort of 84 patients (C-index = 0.707 for the model and 0.721 for the risk score). Conclusions A novel risk stratification strategy can serve as a useful tool for determining prognosis and guide management for medically treated CTEPH patients. Trial registration: ClinicalTrials.gov (Identifier: NCT01417338).

A low specific speed centrifugal compressor with leading/trailing edge combined sweep blades is proposed. The performance and internal flow field characteristics are analyzed in detail by numerical simulations, and a bench test is carried out. It is shown that by using the combined leading/trailing edge swept blade, the stage pressure ratio of the centrifugal compressor is improved under all operating conditions, and the maximum increase can reach 6.5%. The efficiency can be markedly improved at high flow rates. Additionally, the leading edge tip leakage is reduced with the combined swept blade, the flow separation on the blade surface is inhibited, and the flow loss of low-energy flow masses downstream of the flow passage is improved. Meanwhile, the combined swept blade can increase the work area of the blade and enhance the work capacity at the blade tip position.

Abstract Background May-Thurner syndrome (MTS) or Cockett’s syndrome is a rare clinical syndrome, which refers to the compression of the left common iliac vein (LCIV) by right common iliac artery and vertebral body. Complications of MTS include deep vein thrombus formation and even life-threatening pulmonary embolism. Case presentation Here, we report the case of a 60-year-old female patient with a complaint of swelling in the left lower limb and pain for 5 days. Computed tomography angiography indicated MTS, and thrombus formation of left external iliac vein and femoral vein. The patient was diagnosed with deep venous thrombosis (DVT) and MTS. The patient underwent ascending venography from the lower extremity to inferior vena cava (IVC) and then to the pulmonary artery with IVC filter implantation, left iliac vein balloon plasty, and stent placement. The patient visited the hospital for the removal of IVC filter, 28 days after the operation. After the interventional therapy, the patient had no in-stent restenosis and had remission during the 2-year follow-up. Conclusions This case presents a successful management of MTS in presence of DVT. Although clinicians are rarely aware, the presence of unilateral lower limb swelling and thrombosis may be the manifestations of MTS.

Gut microflora plays a key role in host gut health. Unlike feed deprivation, re-feeding has a positive impact on gut health, but their effects on gut microbes remain unclear. Three treatment groups were established in this study to investigate the changes in the gut microbial community and immunity of red swamp crayfish (Procambarus clarkii) under various nutritional states and their functions: Con (the control group, fed for 0 days), Starved (starved for 3 days) and Refed (starved for 3 days, re-fed for 3 days). The results showed that Firmicutes, Bacteroidetes, Deferribacteres and Proteobacteria were the main microbial taxonomy in the gut of P. clarkii. 3-day starvation increased the number of microbial species and their abundance, while the diversity of gut microbes was elevated. The relative abundance of Firmicutes, on the other hand, was significantly reduced, owing to a significant increase in the relative abundance of Deferribacteres (classified as Mucispirillum). 3-day re-feeding restored the number of species and their abundance. Furthermore, starvation induced microbial community disorders by limiting ecological networks and reducing modularity. Re-feeding mitigated the negative effects of starvation on the gut microbial co-occurrence network, increasing the clustering coefficient and the mean network distance, thus maintaining the stability of the gut microbes. Starvation exacerbated the differences in microbial function compared to the control group, while re-feeding restored their function to levels comparable to the control group. Moreover, re-feeding markedly reversed the negative effects of starvation on gut immunity and improved gut health. In conclusion, 3-day starvation disturbed the stability of the gut microbial community, whereas 3-day re-feeding helped to restore the balance of the gut microbial community and its function. It suggested that feed nutrition played an essential role in shaping the gut microbial structure and potentially provided new insights into implications of diet-induced inflammation for gut development in crayfish.

Importance: S100A12 is a calcium binding protein which is involved in inflammation and progression of atherosclerosis.Objective: We sought to investigate the utility of S100A12 as a biomarker for the early diagnosis and prognostication of patients presenting with ST-segment elevation myocardial infarction (STEMI).Design, Setting, and Participants: S100A12 was measured in 1023 patients presenting to the emergency department with acute chest pain between June 2012 and November 2015. An independent cohort of 398 patients enrolled at 3 different hospitals served as a validation cohort.Main Outcomes and Measures: The primary clinical endpoint of interest was major adverse cardiac and cerebral events (MACCE) defined as a composite of all-cause death, MI, stroke, or hospitalization for heart failure.Results: A total of 438/1023 patients (42.8%) in the diagnosis cohort were adjudicated as STEMI, among whom plasma S100A12 levels increased within 30 min and peaked 1–2 h after symptom onset. Compared with high-sensitivity cardiac troponin T and creatine kinase-MB isoenzyme, S100A12 more accurately identified STEMI, especially within the first 2 h after symptom onset (area under the curve 0.963 compared with 0.860 for hscTnT and 0.711 for CK-MB, both P < 0.05). These results were consistent in the 243-patient validation cohort. The 1-year rate of MACCE was greatest in patients in the highest peak S100A12 tertile, intermediate in the middle tertile and least in the lowest tertile (9.3 vs. 5.7 vs. 3.0% respectively, Ptrend = 0.0006). By multivariable analysis the peak plasma concentration of S100A12 was an independent predictor of MACCE within 1 year after STEMI (HR, 1.001, 95%CI, 1.000–1.002; P = 0.0104).Conclusions and Relevance: S100A12 rapidly identified patients with STEMI, more accurately than other cardiac biomarkers, especially within the first 2 h after symptom onset. The peak plasma S100A12 level was a strong predictor of 1-year prognosis after STEMI.

Artificial small-diameter vascular grafts (SDVG) fabricated from synthetic biodegradable polymers, such as poly(ε-caprolactone) (PCL), exhibit beneficial mechanical properties but are often faced with issues impacting their long-term graft success. Nitric oxide (NO) is an important physiological gasotransmitter with multiple roles in orchestrating vascular tissue function and regeneration. We fabricated a functional vascular graft by electrospinning of nitrate-functionalized poly(ε-caprolactone) that could release NO in a sustained manner via stepwise biotransformation in vivo. Nitrate-functionalized SDVG (PCL/NO) maintained patency following abdominal arterial replacement in rats. PCL/NO promoted cell infiltration at 3-months post-transplantation. In contrast, unmodified PCL SDVG showed slow cell in-growth and increased incidence of neointima formation. PCL/NO demonstrated improved endothelial cell (EC) alignment and luminal coverage, and more defined vascular smooth muscle cell (VSMC) layer, compared to unmodified PCL SDVG. In addition, release of NO stimulated Sca-1+ vascular progenitor cells (VPCs) to differentiate and contribute to rapid luminal endothelialization. Furthermore, PCL/NO inhibited the differentiation of VPCs into osteopontin-positive cells, thereby preventing vascular calcification. Overall, PCL/NO demonstrated enhanced cell ingrowth, EC monolayer formation and VSMC layer regeneration; whilst inhibiting calcified plaque formation. Our results suggested that PCL/NO could serve as promising candidates for improved and long-term success of SDVG implants.

Cerebral small vessel disease (SVD) refers to a heterogeneous group of pathological processes that result from damage to the small penetrating vessels in the brain. Spatial navigation, one of the most fundamental behaviors, has lately attracted considerable clinical interest. This study aimed to determine whether spatial navigation performance is impaired in elderly SVD patients. In total, 18 elderly patients with severe SVD, 40 elderly patients with non-severe SVD, and 41 age-matched healthy volunteers were classified according to the Fazekas scale. Spatial navigation was evaluated by Amunet (a computer-based analogy of Morris water maze software), and a mini-mental scale evaluation (MMSE), animal category verbal fluency test (VFT), clock drawing test (CDT), and trail making test (TMT) -B were also applied. Compared to healthy controls, severe SVD, rather than non-severe SVD patients, exhibited significantly worse performance on “allocentric + egocentric” (41.74 ± 29.10 vs. 31.50 ± 16.47 vs. 29.21 ± 19.03; p = 0.031). Furthermore, the different abilities of spatial navigation among groups reached a statistical level on allocentric subtests (46.93 ± 31.27 vs. 43.69 ± 23.95 vs. 28.56 ± 16.38; p = 0.003), but not on egocentric subtest (56.16 ± 39.85 vs. 56.00 ± 28.81 vs. 43.06 ± 25.07; p = 0.105). The linear regression analysis revealed that allocentric navigation deficit was significantly correlated with TMT-B (p = 0.000, standardized β = 0.342) and VFT (p = 0.016, standardized β = −0.873) performance in elderly SVD patients. These results elucidated that spatial navigation ability could be a manifestation of cognitive deficits in elderly patients with SVD.

Idiopathic pulmonary arterial hypertension (IPAH) is a disease with complex etiology. Currently, IPAH treatment is limited, and patients’ prognosis is poor. This study aimed to explore new therapeutic targets in IPAH through bioinformatics. Two data sets (GSE113439 and GSE130391) meeting the requirements were obtained from the Gene Expression Omnibus (GEO) database. Then, differentially expressed genes (DEGs) were identified and analyzed by NetworkAnalyst platform. By enriching Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG), we examined the function of DEGs. A protein–protein interaction (PPI) network was constructed to identify central genes using the CytoNCA plug-in. Finally, four central genes, ASPM, CENPE, NCAPG, and TOP2A, were screened out. We selected NCAPG for protein-level verification. We established an animal model of PAH and found that the expression of NCAPG was significantly increased in the lung tissue of PAH rats. In vitro experiments showed that the expression of NCAPG was significantly increased in proliferative pulmonary arterial smooth muscle cells (PASMCs). When NCAPG of PASMCs was knocked down, the cell proliferation was inhibited, which suggested that NCAPG was related to the proliferation of PASMCs. Therefore, these results may provide new therapeutic targets for IPAH.

Background: To investigate the expression of long non-coding RNA metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) in renal ischemia-reperfusion injury and explore its role in acute kidney injury. Methods: 18 mice were randomly divided into a sham operation group (Sham) and an ischemia-reperfusion group (IR) in which animals were sacrificed at 6 h or 12 h after surgery. The kidneys were harvested to measure the expression of MALAT1 mRNA. HK2 cells were treated with cobalt chloride (CoCl2) to mimic hypoxia or transfected with siRNA to knockdown MALAT1 before CoCl2 treatment. After that, MALAT1 was analyzed by RT-PCR (reverse transcription-polymerase chain reaction). HIF-1ɑ (hypoxia-inducible factor-1 alpha) and NF-κB (nuclear factor-kappa B) was measured by Western blot. The concentrations of IL-6 (interleukin-6) and TNF-ɑ (tumor necrosis factor-alpha) in the media were detected by ELISA (enzyme-linked immunosorbent assay). Results: The expression of MALAT1 in the IR (6 h/12 h) group was significantly higher than that in the sham group. In HK2 cells, MALAT1 was significantly increased at 1 h, 3 h, and 6 h after CoCl2 treatment but had reduced to the basal level at 12 h and 24 h. Knockdown of MALAT1 by siRNA significantly up-regulated the expression of HIF-1ɑ and NF-κB proteins in CoCl2-treated HK2 cells. In addition, the concentrations of IL-6 and TNF-ɑ were increased by MALAT1 siRNA transfection in CoCl2-treated HK2 cells. Conclusion: The expression of MALAT1 is increased in renal ischemia-reperfusion injury. It is likely that MALAT1 inhibits the hypoxia-induced inflammatory response through the NF-κB pathway.

Background: The purpose of this study is to elucidate mechanism(s) by which the orally active PGI2 analog, Beraprost (BPS), ameliorates pulmonary hypertension (PH). Prostaglandins are an important treatment for PH. Mechanisms of their action are not fully elucidated in relation to receptor subtype and effects on O2 sensitive Kv channels.Methods: Distal (3rd order and beyond) pulmonary arteries from chronically hypoxic rats and from humans with established PH were studied. Measurements included pulmonary haemodynamics and histology, vascular reactivity, prostanoid receptor expression and activity of the O2 sensitive Kv channels.Results: Prostacyclin receptor (IP), prostaglandin receptor E3 (EP3) and prostaglandin receptor E4 (EP4) are the main pulmonary artery receptor subtypes in both rat and human pulmonary arteries. Circulating levels of PGI2 and PGE2 were reduced in PH. PH was also associated with reduced receptor expression of IP but not of EP4. The effects on IP expression were overcome with BPS. Dilatory responses in PH to BPS were reduced in the presence of EP4 blockade. Expression and activity of oxygen sensitive Kv channels were reduced in pulmonary artery smooth muscle cell from rats with PH and humans with PAH and were also overcome by administration of BPS. Effects of BPS on oxygen sensitive Kv channels were reduced in the presence of EP4 blockade implicating the EP4 receptor, as well as the IP receptor, in mediating BPS effects.Conclusion: Reduced expression of pulmonary IP receptors and reduced activity of O2 sensitive Kv channels are found in PH in both humans and rats. The orally active prostacyclin analogue, BPS, is able to reverse these changes, partly through binding to the EP4 receptor.

Inadvertent puncture of the subclavian artery is an uncommon but potentially fatal complication of the commonly performed internal jugular vein catheterization. We report a case of accidental subclavian artery catheterization close to the vertebral artery during internal jugular venous cannulation, which was successfully managed in the interventional suite with catheter removal and use of a vascular closure device.