Comparison of genomic prediction methods for early growth traits of Inner Mongolia cashmere goats based on multi trait models.

Inner Mongolia cashmere goat is an excellent livestock breed formed through long-term natural selection and artificial breeding, and is currently a world-class dual-purpose breed producing cashmere and meat. Multi trait animal model is considered to significantly improve the accuracy of genetic evaluation in livestock and poultry, enabling indirect selection between traits. In this study, the pedigree, genotype, environment, and phenotypic records of early growth traits of Inner Mongolia cashmere goats were used to build multi trait animal model., Then three methods including ABLUP, GBLUP, and ssGBLUP wereused to estimate the genetic parameters and genomic breeding values of early growth traits (birth weight, weaning weight, average daily weight gain before weaning, and yearling weight). The accuracy and reliability of genomic estimated breeding value are further evaluated using the five fold cross validation method. The results showed that the heritability of birth weight estimated by three methods was 0.13-0.15, the heritability of weaning weight was 0.13-0.20, heritability of daily weight gain before weaning was 0.11-0.14, and the heritability of yearling weight was 0.09-0.14, all of which belonged to moderate to low heritability. There is a strong positive genetic correlation between weaning weight and daily weight gain before weaning, daily weight gain before weaning and yearling weight, with correlation coefficients of 0.77-0.79 and 0.56-0.67, respectively. The same pattern was found in phenotype correlation among traits. The accuracy of the estimated breeding values by ABLUP, GBLUP, and ssGBLUP methods for birth weight is 0.5047, 0.6694, and 0.7156, respectively; the weaning weight is 0.6207, 0.6456, and 0.7254, respectively; the daily weight gain before weaning was 0.6110, 0.6855, and 0.7357 respectively; and the yearling weight was 0.6209, 0.7155, and 0.7756, respectively. In summary, the early growth traits of Inner Mongolia cashmere goats belong to moderate to low heritability, and the speed of genetic improvement is relatively slow. The genetic improvement of other growth traits can be achieved through the selection of weaning weight. The ssGBLUP method has the highest accuracy and reliability in estimating genomic breeding value of early growth traits in Inner Mongolia cashmere goats, and is significantly higher than that from ABLUP method, indicating that it is the best method for genomic breeding of early growth weight in Inner Mongolia cashmere goats.

Deprotonated 2-thiolimidazole serves as a metal-free electrocatalyst for selective acetylene hydrogenation.

Metal-free catalysts offer a desirable alternative to traditional metal-based electrocatalysts. However, metal-free catalysts, featuring defined active sites, rarely show activities as promising as metal-based materials. Here we report 2-thiolimidazole as an efficient metal-free catalyst for selective electrocatalytic hydrogenation of acetylene into ethylene. Under alkaline conditions, the sulfhydryl and imino groups of 2-thiolimidazole are spontaneously deprotonated into dianions. Deprotonation thus enriches the negative charges of pyridinic N sites in 2-thiolimidazole to enhance the adsorption of electrophilic acetylene through the σ-configuration. Ethylene partial current densities show a volcano relationship with the negative charges of the pyridinic N sites in various imidazole derivatives. Consequently, the deprotonated 2-thiolimidazole exhibits an ethylene partial current density and faradaic efficiency competitive with metal-based catalysts like Cu and Pd. This work highlights the tunability and promising potential of metal-free molecules in electrocatalysis.

Multi-Functional Formaldehyde-Nitrate Batteries for Wastewater Refining, Electricity Generation, and Production of Ammonia and Formate.

As bulky pollutants in industrial and agricultural wastewater, nitrate and formaldehyde pose serious threats to the human health and ecosystem. Current purification technologies including chemical and bio-/photo-/electro-chemical methods, are generally high-cost, time-consuming, or energy-intensive. Here, we report a novel formaldehyde-nitrate battery by pairing anodic formaldehyde oxidation with cathodic nitrate reduction, which simultaneously enables wastewater purification, electricity generation, and the production of high-value-added ammonia and formate. As a result, the formaldehyde-nitrate battery remarkably exhibits an open-circuit voltage of 0.75 V, a peak power density of 3.38 mW cm-2 and the yield rates of 32.7 mg h-1 cm-2 for ammonia and 889.4 mg h-1 cm-2 for formate. In a large-scale formaldehyde-nitrate battery (25 cm2 ), 99.9 % of nitrate and 99.8 % of formaldehyde are removed from simulated industrial wastewater and the electricity of 2.03 W⋅h per day is generated. Moreover, the design of such a multi-functional battery is universally applicable to the coupling of NO3 - or NO2 - reduction with various aldehyde oxidization, paving a new avenue for wastewater purification and chemical manufacturing.

Three-dimensional visualization and evaluation of hilar cholangiocarcinoma resectability and proposal of a new classification.

BACKGROUND: As digital medicine has exerted profound influences upon diagnosis and treatment of hepatobiliary diseases, our study aims to investigate the accuracy of three-dimensional visualization and evaluation (3DVE) system in assessing the resectability of hilar cholangiocarcinoma (hCCA), and explores its potential clinical value. MATERIALS AND METHODS: The discovery cohort, containing 111 patients from April 2013 to December 2019, was retrospectively included to determine resectability according to revised criteria for unresectability of hCCA. 3D visualization models were reconstructed to evaluate resectability parameters including biliary infiltration, vascular involvement, hepatic atrophy and metastasis. Evaluation accuracy were compared between contrast-enhanced CT and 3DVE. Logistic analysis was performed to identify independent risk factors of R0 resection. A new comprehensive 3DVE classification of hCCA based on factors influencing resectability was proposed to investigate its role in predicting R0 resection and prognosis. The main outcomes were also analyzed in cohort validation, including 34 patients from January 2020 to August 2022. RESULTS: 3DVE showed an accuracy rate of 91% (95%CI 83.6-95.4%) in preoperatively evaluating hCCA resectability, significantly higher than 81% (95%CI 72.8-87.7%) of that of CT (p = 0.03). By multivariable analysis, hepatic artery involvement in 3DVE was identified an independent risk factor for R1 or R2 resection (OR = 3.5, 95%CI 1.4,8.8, P < 0.01). New 3DVE hCCA classification was valuable in predicting patients' R0 resection rate (p < 0.001) and prognosis (p < 0.0001). The main outcomes were internally validated. CONCLUSIONS: 3DVE exhibited a better efficacy in evaluating hCCA resectability, compared with contrast-enhanced CT. Preoperative 3DVE demonstrated hepatic artery involvement was an independent risk factor for the absence of R0 margin. 3DVE classification of hCCA was valuable in clinical practice.

[Modification of C20 oxidase in tanshinone biosynthesis pathway].

Tanshinones are one of the main effective components of Salvia miltiorrhiza, which play important roles in the treatment of cardiovascular diseases. Microbial heterogony production of tanshinones can provide a large number of raw materials for the production of traditional Chinese medicine(TCM) preparations containing S. miltiorrhiza, reduce the extraction cost, and relieve the pressure of clinical medication. The biosynthetic pathway of tanshinones contains multiple P450 enzymes, and the catalytic element with high efficiency is the basis of microbial production of tanshinones. In this study, the protein modification of CYP76AK1, a key P450-C20 hydroxylase in tanshinone pathway, was researched. The protein modeling methods SWISS-MODEL, Robetta, and AlphaFold2 were used, and the protein model was analyzed to obtain the reliable protein structure. The semi-rational design of mutant protein was carried out by molecular docking and homologous alignment. The key amino acid sites affecting the oxidation activity of CYP76AK1 were identified by molecular docking. The function of the obtained mutations was studied with yeast expression system, and the CYP76AK1 mutations with continuous oxidation function to 11-hydroxysugiol were obtained. Four key amino acid sites that affected the oxidation acti-vity were analyzed, and the reliability of three protein modeling methods was analyzed according to the mutation results. The effective protein modification sites of CYP76AK1 were reported for the first time in this study, which provides a catalytic element for different oxidation activities at C20 site for the study of the synthetic biology of tanshinones and lays a foundation for the analysis of the conti-nuous oxidation mechanism of P450-C20 modification.

Association of preterm outcome with maternal systemic lupus erythematosus: a retrospective cohort study.

BACKGROUND: Maternal systemic lupus erythematosus (SLE) is at greater risk of pregnancy complications and is associated with increased risk of preterm delivery. However hardly any study has looked at the influence of SLE on the outcomes of preterm infants. This study aimed to explore the influence of SLE on the outcomes of preterm infants. METHODS: In this retrospective cohort study, preterm infants born to mothers with SLE from Shanghai Children's Medical Center during 2012 to 2021 were enrolled. Infants were excluded if they were died during hospitalization or has major congenital anomalies and neonatal lupus. Exposure was defined as mother diagnosed SLE before or during pregnancy. Maternal SLE group was matched with Non-SLE group by gestational age, birth weight and gender. Clinical data has been extracted from patients' records and registered. Major morbidities of premature and biochemical parameters in the two groups were compared using multiple logistic regression. RESULTS: One hundred preterm infants born to 95 mothers with SLE were finally enrolled. The mean (standard deviation) of gestational age and birth weight were 33.09 (7.28) weeks and 1768.50 (423.56) g respectively. There was no significant difference in major morbidities between SLE group and non-SLE group. Compared with non-SLE group, SLE off-spring had significantly lower leukocytes, neutrophiles after birth, neutrophils and platlet in one week (mean difference: -2.825, -2.001, -0.842, -45.469, respectively). Among SLE group, lower birth weight and smaller gestational age were observed in SLE mothers with disease active during pregnancy, kidney involved, blood system involved and not taking Aspirin during pregnancy. In the multivariable logistic regression analysis, exposure to aspirin during pregnancy reduced the risk of very preterm birth and increased the incidence of survive without major morbidities among preterm infants born to SLE mothers. CONCLUSION: Born to mothers with SLE may not increase the risk of major premature morbidities, but the hematologic profile of SLE preterm infants may be different from preterm infants born to women without SLE. The outcome of SLE preterm infants is associated with maternal SLE status and may benefit from maternal aspirin administration.

A Multicenter Study on Preoperative Assessment of Lymphovascular Space Invasion in Early-Stage Cervical Cancer Based on Multimodal MR Radiomics.

BACKGROUND: As lymphovascular space invasion (LVSI) was closely related to lymph node metastasis and prognosis, the preoperative assessment of LVSI in early-stage cervical cancer is crucial for patients. PURPOSE: To develop and validate nomogram based on multimodal MR radiomics to assess LVSI status in cervical cancer patients. STUDY TYPE: Retrospective. POPULATION: The study included 168 cervical cancer patients, of whom 129 cases (age 51.36 ± 9.99 years) from institution 1 were included as the training cohort and 39 cases (age 52.59 ± 10.23 years) from institution 2 were included as the external test cohort. FIELD STRENGTH/SEQUENCE: There were 1.5 T and 3.0 T MRI scans (T1-weighted imaging [T1WI], fat-saturated T2-weighted imaging [FS-T2WI], and contrast-enhanced [CE]). ASSESSMENT: Six machine learning models were built and selected to construct the radiomics signature. The nomogram model was constructed by combining the radiomics signature with the clinical signature, which was then validated for discrimination, calibration, and clinical usefulness. STATISTICAL TESTS: The clinical characteristics were compared using t-tests, Mann-Whitney U tests, or chi-square tests. The Spearman and LASSO methods were used to select radiomics features. The receiver operating characteristic (ROC) analysis was performed, and the area under the curve (AUC), accuracy, sensitivity, and specificity were calculated. RESULTS: The logistic regression (LR) model performed best in each sequence. The AUC of CE-T1-T2WI-combined was the highest in the LR model, with an AUC of 0.775 (95% CI: 0.570-0.979) in external test cohort. The nomogram showed high predictive performance in the training (AUC: 0.883 [95% CI: 0.823-0.943]) and test cohort (AUC: 0.830 [95% CI: 0.657-1.000]) for predicting LVSI. Decision curve analysis demonstrated that the nomogram was clinically useful. DATA CONCLUSION: Our findings suggest that the proposed nomogram model based on multimodal MRI of CE T1WI-T2WI-combined could be used to assess LVSI status in early cervical cancer. EVIDENCE LEVEL: 4. TECHNICAL EFFICACY: Stage 2.

Highly selective electrocatalytic alkynol semi-hydrogenation for continuous production of alkenols.

Alkynols semi-hydrogenation is a critical industrial process as the product, alkenols, have extensive applications in chemistry and life sciences. However, this class of reactions is plagued by the use of high-pressure hydrogen, Pd-based catalysts, and low efficiency of the contemporary thermocatalytic process. Here, we report an electrocatalytic approach for selectively hydrogenating alkynols to alkenols under ambient conditions. For representative 2-methyl-3-butene-2-ol, Cu nanoarrays derived electrochemically from CuO, achieve a high partial current density of 750 mA cm-2 and specific selectivity of 97% at -0.88 V vs. reversible hydrogen electrode in alkaline solution. Even in a large two-electrode flow electrolyser, the Cu nanoarrays deliver a single-pass alkynol conversion of 93% with continuous production of 2-methyl-3-butene-2-ol at a rate of ~169 g gCu-1 h-1. Theoretical and in situ electrochemical infrared investigations reveal that the semi-hydrogenation performance is enhanced by exothermic alkynol adsorption and alkenol desorption on the Cu surfaces. Furthermore, this electrocatalytic semi-hydrogenation strategy is shown to be applicable to a variety of alkynol substrates.

[Identification of genes involved in biosynthesis of paeoniflorin in Paeonia lactiflora based on transcriptome analysis].

Paeoniflorin, a representative pinane monoterpene glycoside, is the main active component and quality index of Paeoniae Radix Alba and Paeoniae Radix Rubra.The possible biosynthesis of paeoniflorin is as follows: GPP is derived from mevalonate(MVA) and/or 2-C-methyl-D-erythritol 4-phosphate(MEP) pathway(s) followed by the catalysis with terpene synthase, cytochrome P450(CYP450), UDP-glucuronosyltransferase(UGT), and acyltransferase(AT), respectively.This study aims to explore the genes rela-ted to the biosynthesis of paeoniflorin.To be specific, the cDNA libraries for flowers, leaves, and roots of Paeonia lactiflora were established and sequenced.A total of 30 609 open reading frames(ORFs) were yielded.Through functional annotation and expression analysis of all CYP450 genes in the transcriptome, 11 CYP450 genes belonging to CYP71 A and CYP71 D subfamilies and showing expression trend consistent with monoterpene synthase PlPIN that may be involved in paeoniflorin biosynthesis were screened out.Subsequently, 7 UGT genes and 9 AT genes demonstrating the expression trend consistent with PlPIN which were possibly involved in paeoniflorin biosynthesis were further screened by functional annotation analysis, full-length sequence analysis, expression analysis, and phylogeny analysis.This study provided a systematic screening method with smaller number of candidate genes, thus reducing the workload of functional gene verification.The result laid a foundation for analyzing the biosynthesis pathway of paeoniflorin and the formation mechanism.

New roles of DNA-binding and forkhead-associated domains of Fkh1 and Fkh2 in cellular functions.

Two yeast forkhead transcription factors Fkh1 and Fkh2 regulate the transcription of CLB2 cluster genes important for mitosis. Both proteins contain a DNA-binding domain (DBD) and a forkhead-associated domain (FHAD), which are essential for ternary complex formation with transcription factor Mcm1, the transcription of CLB2 cluster genes and the physical interaction with Ndd1 and Clb2. Fkh2 also contains an additional C' domain that contains six consensus Cdk phosphorylation sites, but the function of this domain is dispensable. Here, we found new roles of the DBD, the FHAD, and the C' domain of Fkh1 and Fkh2 in cellular functions. The Fkh2 DBD determines the genetic interaction with NDD1, while both the FHAD and DBD of Fkh1 or Fkh2 determine cell morphology and stability of their own transcripts. Both HFADs, but not DBDs, also mediate physical interaction between Fkh1 and Fkh2. DBD and HFAD of Fkh1 and DBD, but not HFAD, of Fkh2 are also fundamental for nuclear localization. However, the Fkh2-specific C' domain has no role in these aspects except in the stability of some fkh mutant transcripts, which is either increased or decreased in the presence of this domain. These findings reveal that Fkh1 and Fkh2 have multiple cellular functions and function mainly via their DBD and FHAD through a domain-controlled feedback regulation mechanism.

Preparation and Properties of Double Network Hydrogel with High Compressive Strength.

In this work, p-double network (p-DN) hydrogels were formed by the interpenetration of poly(2-acrylamide-2-methylpropanesulfonic acid-copolymer- acrylamide) microgel and polyacrylamide. The initial viscosity of prepolymer solution before hydrogel polymerization, mechanical properties, temperature and salt resistance of the hydrogels were studied. The results showed that the initial viscosity of the prepolymer was less than 30 mP·s, and the p-DN hydrogel not only exhibited high compressive stress (37.80 MPa), but the compressive strength of p-DN hydrogel could also reach 23.45 MPa after heating at 90 °C, and the compressive strength of p-DN hydrogel could reach 13.32 MPa after soaking for 24 h in the solution of 5W mineralization. In addition, the cyclic loading behavior of hydrogel was studied. The dissipation energy of p-DN hydrogel under 80% strain was 7.89 MJ/m3, which effectively dissipated energy. Meanwhile, p-DN hydrogel maintained its original form while breaking the pressure greater than 30 MPa, indicating excellent plugging performance.

Functional Aqueous Zinc-Acetylene Batteries for Electricity Generation and Electrochemical Acetylene Reduction to Ethylene.

The available processes for removing acetylene impurities from crude ethylene are tremendously energy-intensive. Herein, we demonstrate a novel aqueous Zn-C2 H2 battery, which not only switches energy-consuming acetylene removal to electricity generation, but also reduces acetylene to ethylene through a unique discharge mechanism: C2 H2 +Zn+H2 O→C2 H4 +ZnO. Under a pure acetylene stream, this Zn-C2 H2 battery exhibits an open circuit potential of 1.14 V and a peak power density of 2.2 mW cm-2 , which exceed those of reported Zn-CO2 batteries. Even for simulated crude ethylene, the Zn-C2 H2 battery manifests an acetylene conversion of 99.97 % and continuously produces polymer-grade ethylene with only ≈3 ppm acetylene during a long-term discharge operation. Such a functional battery is universally appliable for reducing other alkynes and generating electricity. Therefore, this work provides an effective strategy for green ethylene purification and the design of functional batteries.

Effect of laparoscopic surgery for colorectal cancer with N. O. S. E. on recovery and prognosis of patients.

OBJECTIVE: To investigate the effect of laparoscopic surgery in colorectal cancer (CRC) patients with natural orifice specimen extraction (NOSE) on the recovery and quality of life (QOL) of patients. MATERIAL AND METHODS: Ninety-two eligible patients were randomly assigned into two groups: the traditional laparoscopy group (L group, n = 46) and the laparoscopic transanal specimen extraction group (NL group, n = 46). General data, surgery-related indicators, postoperative recovery, and prognosis were compared and analyzed between the two groups. RESULTS: A total of 46 patients in each group were enrolled in this study. The general data and surgery-related indicators were comparable between the two groups (all p > .05). There were no significant differences in the time of first flatus, bleeding, obstruction, constipation, and infectious complications between the two groups (all p > .05). The differences in the incidence of postoperative diarrhea, pain degree, and satisfaction on the aesthetics of the abdominal wall showed significant differences (χ2 = 6.133, p = .013; χ2 = 12.116, p = .017; χ2 = 13.463, p = .004). The postoperative follow-up time was 3-53 months. There were no significant differences in the postoperative hospital stay, medical costs, hospital readmission rate, incidence of incisional hernia, overall survival, disease-free survival, and QOL between the two groups (all p > .05). Conclusion: Laparoscopic surgery with NOSE for eligible patients with CRC was a feasible choice.

Nonplanar Helicene Benzo[4]Helicenium for the Precise Treatment of Renal cell Carcinoma.

Immune and targeted therapy are becoming the first-line treatment for renal cell carcinoma (RCC). However, therapeutic outcomes are limited due to the low efficiency and side effect. Here, it is found that helicenes are able to exhibit an anticancer capability through changing the molecular structure from planar to nonplanar. Furthermore, the cytotoxicity in vitro and cancer inhibition ability of nonplanar helicenes increase with its aromatic rings' number. It is further demonstrated that benzo[4]helicenium shows the specific killing efficiency against the RCC cancer as compared to normal kidney cells. This is majorly originated from a more selective damage of benzo[4]helicenium for mitochondria and DNA in RCC cancer cells, not the normal kidney. The selective killing ability of benzo[4]helicenium makes it have potential to be used as a targeted drug for the precise treatment of RCC.

The Value of Predicting Human Epidermal Growth Factor Receptor 2 Status in Adenocarcinoma of the Esophagogastric Junction on CT-Based Radiomics Nomogram.

PURPOSE: We developed and validated a CT-based radiomics nomogram to predict HER2 status in patients with adenocarcinoma of esophagogastric junction (AEG). METHOD: A total of 101 patients with HER2-positive (n=46) and HER2-negative (n=55) esophagogastric junction adenocarcinoma (AEG) were retrospectively analyzed. They were then randomly divided into a training cohort (n=70) and a verification cohort (n=31). The radiomics features were obtained from the portal phase of the CT enhanced scan. We used the least absolute shrinkage and selection operator (LASSO) logistic regression method to select the best radiomics features in the training cohort, combined them linearly, and used the radiomics signature formula to calculate the radiomics score (Rad-score) of each AEG patient. A multivariable logistic regression method was applied to develop a prediction model that incorporated the radiomics signature and independent risk predictors. The prediction performance of the nomogram was evaluated using the training and validation cohorts. RESULT: In the training (P<0.001) and verification groups (P<0.001), the radiomics signature combined with seven radiomics features was significantly correlated with HER2 status. The nomogram composed of CT-reported T stage and radiomics signature showed very good predictive performance for HER2 status. The area under the curve (AUC) of the training cohort was 0.946 (95% CI: 0.919-0.973), and that of the validation group was 0.903 (95% CI: 0.847-0.959). The calibration curve of the radiomics nomogram showed a good degree of calibration. Decision-curve analysis revealed that the radiomics nomogram was useful. CONCLUSION: The nomogram CT-based radiomics signature combined with CT-reported T stage can better predict the HER2 status of AEG before surgery. It can be used as a non-invasive prediction tool for HER2 status and is expected to guide clinical treatment decisions in clinical practice, and it can assist in the formulation of individualized treatment plans.

Efficient electrocatalytic acetylene semihydrogenation by electron-rich metal sites in N-heterocyclic carbene metal complexes.

Electrocatalytic acetylene semihydrogenation is a promising alternative to thermocatalytic acetylene hydrogenation due to its environmental benignity and economic efficiency, but its performance is far below that of the thermocatalytic reaction because of strong competition from side reactions, including hydrogen evolution, overhydrogenation and carbon-carbon coupling reactions. We develop N-heterocyclic carbene-metal complexes, with electron-rich metal centers owing to the strongly σ-donating N-heterocyclic carbene ligands, as electrocatalysts for selective acetylene semihydrogenation. Experimental and theoretical investigations reveal that the copper sites in N-heterocyclic carbene-copper facilitate the absorption of electrophilic acetylene and the desorption of nucleophilic ethylene, ultimately suppressing the side reactions during electrocatalytic acetylene semihydrogenation, and exhibit superior semihydrogenation performance, with faradaic efficiencies of ≥98 % under pure acetylene flow. Even in a crude ethylene feed containing 1 % acetylene (1 × 104 ppm), N-heterocyclic carbene-copper affords a specific selectivity of >99 % during a 100-h stability test, continuous ethylene production with only ~30 ppm acetylene, a large space velocity of up to 9.6 × 105 mL·gcat-1·h-1, and a turnover frequency of 2.1 × 10-2 s-1, dramatically outperforming currently reported thermocatalysts.

Regulating Water Reduction Kinetics on MoP Electrocatalysts Through Se Doping for Accelerated Alkaline Hydrogen Production.

Owing to its low cost, high conductivity, and chemical stability, Molybdenum phosphide (MoP) has great potential for electrochemically catalyzing the hydrogen evolution reaction (HER). Unfortunately, the development of high-activity MoP still remains a grand challenge in alkali-electrolyzers due to its sluggish water reduction kinetics. Here, we demonstrate a novel strategy for regulating the HER kinetics of the MoP nanowire cathode through partially substituting P atoms with Se dopants. In alkaline solutions, the Se-doped MoP (Se-MoP) nanowire cathode exhibits excellent HER performance with a greatly-decreased overpotential of ∼61 mV at 10 mA cm-2 and a Tafel slope of ∼63 mV dec-1, outperforming currently reported MoP-based electrocatalysts. Experimental and theoretical investigations reveal that Se doping not only facilitates the water dissociation on MoP, but also optimize the hydrogen adsorption free energy, eventually speeding up the sluggish alkaline HER kinetics. Therefore, this work paves a new path for designing MoP-based electrocatalyst with high HER performance in alkaline electrolyzers.

Thymosin ß4 increases cardiac cell proliferation, cell engraftment, and the reparative potency of human induced-pluripotent stem cell-derived cardiomyocytes in a porcine model of acute myocardial infarction.

Rationale: Previous studies have shown that human embryonic stem cell-derived cardiomyocytes improved myocardial recovery when administered to infarcted pig and non-human primate hearts. However, the engraftment of intramyocardially delivered cells is poor and the effectiveness of clinically relevant doses of human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) in large animal models of myocardial injury remains unknown. Here, we determined whether thymosin ß4 (Tb4) could improve the engraftment and reparative potency of transplanted hiPSC-CMs in a porcine model of myocardial infarction (MI). Methods: Tb4 was delivered from injected gelatin microspheres, which extended the duration of Tb4 administration for up to two weeks in vitro. After MI induction, pigs were randomly distributed into 4 treatment groups: the MI Group was injected with basal medium; the Tb4 Group received gelatin microspheres carrying Tb4; the CM Group was treated with 1.2 × 108 hiPSC-CMs; and the Tb4+CM Group received both the Tb4 microspheres and hiPSC-CMs. Myocardial recovery was assessed by cardiac magnetic resonance imaging (MRI), arrhythmogenesis was monitored with implanted loop recorders, and tumorigenesis was evaluated via whole-body MRI. Results: In vitro, 600 ng/mL of Tb4 protected cultured hiPSC-CMs from hypoxic damage by upregulating AKT activity and BcL-XL and promoted hiPSC-CM and hiPSC-EC proliferation. In infarcted pig hearts, hiPSC-CM transplantation alone had a minimal effect on myocardial recovery, but co-treatment with Tb4 significantly enhanced hiPSC-CM engraftment, induced vasculogenesis and the proliferation of cardiomyocytes and endothelial cells, improved left ventricular systolic function, and reduced infarct size. hiPSC-CM implantation did not increase incidence of ventricular arrhythmia and did not induce tumorigenesis in the immunosuppressed pigs. Conclusions: Co-treatment with Tb4-microspheres and hiPSC-CMs was safe and enhanced the reparative potency of hiPSC-CMs for myocardial repair in a large-animal model of MI.

Myocardial area at risk and salvage in reperfused acute MI measured by texture analysis of cardiac T2 mapping and its prediction value of functional recovery in the convalescent stage.

OBJECTIVES: We sought to distinguish area at risk from salvage myocardial zone and to predict left ventricle functional recovery in the convalescent stage by Texture Analysis (TA) of T2-Mapping. METHODS: One hundred and six patients diagnosed with AMI and treated with percutaneous coronary intervention (PCI) underwent acute cardiac magnetic resonance imaging (CMR) and 45 of whom had a subsequent CMR scan following recovery. Cine imaging, T2-Mapping, T2-weighted STIR imaging, and LGE imaging were performed. In the texture analysis, regions of interest (infarcted, salvageable, and remote) were drawn by two blinded, independent readers. RESULTS: Seven independent texture features on T2-Mapping were selected: Perc.50%, S(2,2)InvDfMom, S(2.-2)AngScMom, S(4,0)Entropy, 45dgrLngREmph, 45dgr_Fraction and 135dr_GLevNonU. Among them, the average value of 135dr_GLevNonU in the infarct zone, AAR zone, and the remote zone was: 61.96±26.03, 31.811±18.933 and 99.839±26.231, respectively. Additionally, 135dr_GLevNonU provided the highest area under the curve (AUC) from the receiver operating characteristic curve (ROC curve) for distinguishing AAR from the infarct zone in each subgroup (all patients, patients with MVO and)were 0.845 ± 0.052 0.855 ± 0.083 and 0.845 ± 0.066, respectively, and were more promise than T2-Mapping mean (p<0.001). The AUC for differentiating AAR from the remote zone is 0.942±0.041. Texture features are not associated with convalescent decreased strain, ejection fraction (EF) or left ventricle remodeling (LVR) in analysis (p>0.05). CONCLUSION: TA of T2-mapping can distinguish AAR from both the infarct zone and the remote myocardial zone without LGE imaging in reperfused AMI. However, these features are not able to predict patients' functional recovery in the convalescent stage.

One vector-based method to verify predicted plant miRNAs, target sequences, and function modes.

Many microRNAs (miRNAs) have been predicted from small RNA sequencing data, but little was experimentally verified due to the lack of effective methods. Here, we developed a simple and reliable dual gene expression cassette vector-based method to verify predicted plant miRNAs. We cloned osa-miR528 as a known miRNA, hvu-miRX as a predicted miRNA and TaDREB3 open reading frame as a non-miRNA into the first gene expression cassette and fused their complementary or noncomplementary sequences as predicted target or nontarget sequences with the 3' untranslated region of green fluorescent protein (GFP) in the second one. When these constructs were bombarded into plant cells, only the construct containing both osa-miR528 or hvu-miRX and its complementary sequence did not generate green fluorescence. Stem-loop reverse-transcription polymerase chain reaction detected mature osa-miR528 or mature hvu-miRX in the cells, while northern analysis showed that GFP messenger RNA from the construct containing both osa-miR528 or hvu-miRX and its complementary sequence was degraded. Taken together, the results indicate that hvu-miRX is an authentic miRNA like osa-miR528, miRNA's complementary sequence is its target sequence, and both osa-miR528 and hvu-miRX silenced the GFP expression via a cleavage mode. Our method thus facilitates the verification of predicted plant miRNAs, target sequences, and function modes.