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Poly ADP ribose polymerase (PARP) inhibitors have led to a step change in the management of advanced ovarian cancer following the first approval of these inhibitors in 2014. PARP is an enzyme needed for DNA repair and its inhibition results in the accumulation of single-strand DNA breaks. PARP inhibitors were initially hypothesized to have maximum efficacy in ovarian cancer with BRCA1/2 mutations or homologous recombination (HR) deficiency (HRD) ) given the role of these pathways in repairing double-stranded DNA breaks. The accumulation of both single-strand and double-strand breaks would result in synthetic lethality and preferential cancer cell cytotoxicity with BCRA1/2 mutations and HRD being a predictive biomarker of response. Here we present data that patients with recurrent ovarian cancer will benefit from PARP inhibitors, given as maintenance therapy irrespective of BRCA or HR status. This has been shown with olaparib, niraparib, and rucaparib; all three PARP inhibitors are licensed for the treatment of recurrent ovarian cancer following a response to platinum-based therapy in both BRCA-mutant and wild-type patients.
The new mineral, gysinite-(La), with the ideal formula PbLa(CO3)2(OH)⋅H2O, has been discovered in lujavrite from the Saima alkaline complex, Liaoning Province, China. It commonly occurs as subhedral to anhedral, granular and platy crystals of 5 to 50 μm in size, in interstices or enclosed in microcline, aegirine and nepheline. Associated minerals include nepheline, aegirine, microcline, natrolite, eudialyte, lamprophyllite, bastnäsite-(Ce), parasite-(Ce), ancylite-(La), ancylite-(Ce), bobtraillite, britholite-(Ce), thorite, calcite and galena. The crystallisation of gysinite-(La) may be related to the post-magmatic carbonation event. Gysinite-(La) crystals are generally transparent, colourless, or pale yellow, with a vitreous lustre and white streak. It is brittle with an uneven fracture, and the estimated Mohs hardness is 3½ to 4. The calculated density is 5.007 g/cm3. Optically, gysinite-(La) is biaxial (–), α= 1.832(2), β= 1.849(4), γ = 1.862(5) in white light and 2Vmeas = 81.6°. The empirical formula of gysinite-(La) is (La0.93Pb0.61Nd0.23Pr0.14Sr0.04Gd0.02Sm0.01Eu0.01Ca0.01)Σ2(CO3)2(OH)1.34⋅0.66H2O, which is calculated on the basis of general formula (REExM2+2–x)(CO3)2(OH)x⋅(2–x)H2O. The strongest eight lines of its powder X-ray diffraction pattern [d, Å (I, %) (hkl)] are: 5.596 (21) (011), 4.349 (100) (110), 3.732 (68) (111), 2.984 (61) (121), 2.667 (21) (031), 2.363 (48) (131), 2.090 (29) (221) and 2.028 (21) (212). Gysinite-(La) is orthorhombic, in the space group Pmcn, and unit-cell parameters refined from single-crystal X-ray diffraction data are: a = 5.0655(2) Å, b = 8.5990(3) Å, c = 7.3901(4) Å, V = 321.90(2) Å3 and Z = 2. It is a new member of the ancylite group and isostructural with gysinite-(Nd), but with La and Pb dominant in the metal cation sites in the structure.
It has been suggested that added sugar intake is associated with non-alcoholic fatty liver disease (NAFLD). However, previous studies only focused on sugar-sweetened beverages; the evidence for associations with total added sugars and their sources is scarce. This study aimed to examine the associations of total added sugars, their physical forms (liquid v. solid) and food sources with risk of NAFLD among adults in Tianjin, China. We used data from 15 538 participants, free of NAFLD, other liver diseases, CVD, cancer or diabetes at baseline (2013–2018 years). Added sugar intake was estimated from a validated 100-item FFQ. NAFLD was diagnosed by ultrasonography after exclusion of other causes of liver diseases. Multivariable Cox proportional hazards models were fitted to calculate hazard ratios (HR) and corresponding 95 % CI for NAFLD risk with added sugar intake. During a median follow-up of 4·2 years, 3476 incident NAFLD cases were documented. After adjusting for age, sex, BMI and its change from baseline to follow-up, lifestyle factors, personal and family medical history and overall diet quality, the multivariable HR of NAFLD risk were 1·18 (95 % CI 1·06, 1·32) for total added sugars, 1·20 (95 % CI 1·08, 1·33) for liquid added sugars and 0·96 (95 % CI 0·86, 1·07) for solid added sugars when comparing the highest quartiles of intake with the lowest quartiles of intake. In this prospective cohort of Chinese adults, higher intakes of total added sugars and liquid added sugars, but not solid added sugars, were associated with a higher risk of NAFLD.
Fluorsigaiite, ideally Ca2Sr3(PO4)3F, is a new Sr analogue of fluorphosphohedyphane and a new member of the apatite supergroup. It was discovered in lujavrite from the Saima alkaline complex, Liaoning Province, China. Fluorsigaiite commonly occurs as individual prismatic, columnar and platy crystals of 10 to 50 μm in size, associated with microcline, nepheline, aegirine, natrolite, eudialyte, fluorapatite, a fluorstrophite-like mineral, stronadelphite and calcite. Occasionally, crystals of fluorsigaiite form prismatic aggregates in the interstices of lujavrite. Fluorsigaiite is translucent to transparent, colourless to yellowish white with a vitreous lustre and without fluorescence. The estimated Mohs hardness is 5, and the tenacity is brittle with uneven fractures. The calculated density is 3.842 g/cm3. Optically, fluorsigaiite is uniaxial (–) with ω = 1.64(1) and ɛ = 1.63(1) in white light and without dispersion. The mean chemical composition (in wt.%) of fluorsigaiite is Na2O 0.75, CaO 15.17, SrO 44.44, La2O3 3.64, Ce2O3 2.22, Pr2O3 0.19, Nd2O3 0.13, Sm2O3 0.05, Gd2O3 0.23, P2O5 31.87, F 1.91, H2O 0.46, sum 100.26, giving the empirical formula (Sr2.82Ca1.79Na0.16La0.15Ce0.09Pr0.01Nd0.01Gd0.01)Σ5.04P2.97O12[F0.66(OH)0.34]Σ1, which is calculated on the basis of 13 total anions and F+(OH) = 1. The strongest eight lines of its powder X-ray diffraction pattern [d, Å (I, %) (hkl)] are: 3.563 (15) (002), 3.275 (15) (102), 3.144 (19) (120), 2.876 (100) (121), 2.861 (96) (112), 2.772 (27) (300), 1.991 (17) (222) and 1.895 (23) (213). Fluorsigaiite is hexagonal, in the space group P63/m and unit-cell parameters refined from single-crystal X-ray diffraction data are: a = 9.6101(2) Å, c = 7.1311(1) Å, V = 570.35(3) Å3 and Z = 2. It is isostructural with hedyphane-group minerals, and contains different prevailing (species-defining) Ca and Sr cations at the Ca1 and Ca2 sites, respectively. Fluorsigaiite was probably formed from Sr-rich fluids at late-magmatic or hydrothermal stage of the Saima lujavrite.
Late Palaeozoic igneous rock associations in response to subduction, accretion, and final closure of the eastern Palaeo-Asian Ocean play a significant role in understanding the geodynamic evolution of the southeastern Central Asian Orogenic Belt. Previous studies have identified a Permian arc magmatic belt associated with the southward-dipping subduction of the eastern Palaeo-Asian Ocean along the Solonker–Changchun suture zone. The genetic mechanism and associated geodynamic settings are of great importance in deciphering the evolution of the eastern Palaeo-Asian Ocean. This paper presents zircon U–Pb–Hf isotope and whole-rock geochemical analyses for a suite of magmatic rocks including the early Permian diorite porphyrites (ca. 281.0 Ma), andesites (ca. 276 Ma) and rhyolites (ca. 275 Ma) in the Kulun region. The diorite porphyrites and andesites have high SiO2 and total alkali contents, and low MgO contents and Mg no. values, with enrichments in large ion lithophile elements and depletions in high-field-strength elements. These geochemical characteristics, together with low-Sr and high-Yb contents, a weak concave-upward shape of middle rare earth elements and negative Eu anomalies, suggest that these intermediate igneous rocks were generated by partial melting of amphibolitic lower crust at a crustal depth of 30–40 km. The rhyolites have heterogeneous isotopic compositions, with ϵHf(t) values and TDM2 ages of –20.8 to +0.5 and 3578∼1494 Ma, implying that they were likely derived from partial melting of a mixed source dominated by recycled ancient crust with minor juvenile crustal materials. The rhyolites show potassic affinity with relatively high K2O and very low Na2O, which was attributed to liquid immiscibility of felsic magma and subsequent limited fractional crystallization of plagioclase. The regional igneous associations, metamorphic events, and coeval sedimentary rocks along the Solonker–Changchun suture zone indicate that the early Permian igneous rocks were formed in an active continental arc environment in response to southward subduction of the eastern Palaeo-Asian Ocean.
Prospective cohort studies linking organ meat consumption and non-alcoholic fatty liver disease (NAFLD) are limited, especially in Asian populations. This study aimed to prospectively investigate the association between organ meat consumption and risk of NAFLD in a general Chinese adult population. This prospective cohort study included a total of 15 568 adults who were free of liver disease, CVD and cancer at baseline. Dietary information was collected at baseline using a validated FFQ. NAFLD was diagnosed by abdominal ultrasound after excluding other causes related to chronic liver disease. Cox proportional regression models were used to assess the association between organ meat consumption and risk of NAFLD. During a median of 4·2 years of follow-up, we identified 3604 incident NAFLD cases. After adjusting for demographic characteristics, lifestyle factors, vegetable, fruit, soft drink, seafood and red meat consumption, the multivariable hazard ratios (95 % CI) for incident NAFLD across consumption of organ meat were 1·00 (reference) for almost never, 1·04 (0·94, 1·15) for tertile 1, 1·08 (0·99, 1·19) for tertile 2 and 1·11 (1·01, 1·22) for tertile 3, respectively (Pfor trend < 0·05). Such association did not differ substantially in the sensitivity analysis. Our study indicates that organ meat consumption was related to a modestly higher risk of NAFLD among Chinese adults. Further investigations are needed to confirm this finding.
Primitive lamprophyres in orogenic belts can provide crucial insights into the nature of the subcontinental lithosphere and the relevant deep crust–mantle interactions. This paper reports a suite of relatively primitive lamprophyre dykes from the North Qiangtang, central Tibetan Plateau. Zircon U–Pb ages of the lamprophyre dykes range from 214 Ma to 218 Ma, with a weighted mean age of 216 ± 1 Ma. Most of the lamprophyre samples are similar in geochemical compositions to typical primitive magmas (e.g. high MgO contents, Mg no. values and Cr, with low FeOt/MgO ratios), although they might have experienced a slightly low degree of olivine crystallization, and they show arc-like trace-element patterns and enriched Sr–Nd isotopic composition ((87Sr/86Sr)i = 0.70538–0.70540, ϵNd(t) = −2.96 to −1.65). Those geochemical and isotopic variations indicate that the lamprophyre dykes originated from partial melting of a phlogopite- and spinel-bearing peridotite mantle modified by subduction-related aqueous fluids. Combining with the other regional studies, we propose that slab subduction might have occurred during Late Triassic time, and the rollback of the oceanic lithosphere induced the lamprophyre magmatism in the central Tibetan Plateau.
Solid solution 0.94Na0.5Bi0.5TiO3–6BaTiO3 (NBT–6BT) is considered to be one kind of lead-free piezoelectric materials with excellent electrical properties due to the existence of morphotropic phase boundary (MPB). However, its relatively lower depolarization temperature is a long-standing bottleneck for the application of NBT-based piezoelectric ceramics. In this work, the influence of thermal quenching on depolarization temperature and electrical properties of rare-earth Ho-doped NBT–6BT lead-free ceramics was investigated. It was shown that the relative high piezoelectric performance, as well as an improvement of depolarization temperature (Td), can be realized by thermal quenching. The results showed that the quenching process induced high concentration of oxygen vacancy, giving rise to the change of octahedra mode and enhanced lattice distortion, which is benefit to the temperature stability of piezoelectric and ferroelectric properties. Furthermore, up-conversion photoluminescence (PL) of Ho-doped NBT–6BT could be effectively tuned by the introduction of oxygen vacancy, suggesting a promising potential in optical–electrical multifunctional devices.
We document the central role of collateral in the pricing of tri-party repos. Markets are competitive for repos with safe collateral but are severely segmented for repos with risky collateral, such as equities and low-grade corporate bonds. Fund families are the sole contributors to the segmentation, and collateral concentration is the main determinant in the substantial variation in repo pricing, both across and within segments. The segmented structure points to Fidelity as a systemically important player and the markets potential fragility. Facing market segmentation, dealers optimize financing costs by allocating their collateral across fund families.
Our present genetic data of Acanthocephala, especially the mitochondrial (mt) genomes, remains very limited. In the present study, the nearly complete mt genome sequences of Sphaerirostris lanceoides (Petrochenko, 1949) was sequenced and determined for the first time based on specimens collected from the Indian pond heron Ardeola grayii (Sykes) (Ciconiiformes: Ardeidae) in Pakistan. The mt genome of S. lanceoides is 13 478 bp in size and contains 36 genes, including 12 protein-coding genes (PCGs), 22 transfer RNA genes (tRNAs) and two ribosomal RNA genes (rRNAs). Moreover, in order to clarify the phylogenetic relationship of the genera Centrorhynchus and Sphaerirostris, and to test the systematic position of S. lanceoides in the Centrorhynchidae, the phylogenetic analyses were performed using Bayesian inference and maximum likelihood methods, based on concatenated nucleotide sequences of 12 PCGs, rRNAs and tRNAs. The phylogenetic results further confirmed the monophyly of the order Polymorphida and the paraphyly of the order Echinorhynchida in the class Palaeacanthocephala. Our results also challenged the validity of the genus Sphaerirostris (Polymorphida: Centrorhynchidae) and showed a sister relationship between S. lanceoides and S. picae (Rudolphi, 1819).
The effects of macronutrient intake on obesity are controversial. This research aims to investigate the associations between macronutrient intake and new-onset overweight/obesity. The relationship between the consumption of carbohydrate and total fat and obesity was assessed by the multivariable Cox model in this 11-year cohort, which included 6612 adults (3291 men and 3321 women) who were free of overweight and obesity at baseline. The dietary intake was recorded using a 24-h recall method for three consecutive days. Moreover, substitution models were developed to distinguish the effects of macronutrient composition alteration from energy intake modification. During 7·5 person years (interquartile range 4·3, 10·8) of follow-up, 1807 participants became overweight or obese. After adjusting for risk factors, the hazard ratio (HR) of overweight/obesity in extreme quintiles of fat was 1·48 (quintile 5 v. quintile 1, 95 % CI 1·16, 1·89; Ptrend = 0·02) in women. Additionally, replacing 5 % of energy from carbohydrate with equivalent energy from fat was associated with an estimated 4·3 % (HR 1·043, 95 % CI 1·007, 1·081) increase in overweight/obesity in women. Moreover, dietary carbohydrate was inversely associated with overweight/obesity (quintile 5 v. quintile 1, HR 0·70, 95 % CI 0·55, 0·89; Ptrend = 0·02) in women. Total fat was related to a higher risk of overweight/obesity, whereas high carbohydrate intake was related to a lower risk of overweight/obesity in women, which was not observed in men.
The aim of this study was to analyze the profile of chest injuries, oxygen therapy for respiratory failure, and the outcomes of victims after the Jiangsu tornado, which occurred on June 23, 2016 in Yancheng City, Jiangsu Province, China.
The clinical records of 144 patients referred to Yancheng City No.1 People’s Hospital from June 23 through June 25 were retrospectively investigated. Of those patients, 68 (47.2%) sustained major chest injuries. The demographic details, trauma history, details of injuries and Abbreviated Injury Scores (AIS), therapy for respiratory failure, surgical procedures, length of intensive care unit (ICU) and hospital stay, and mortality were analyzed.
Of the 68 patients, 41 (60.3%) were female and 27 (39.7%) were male. The average age of the injured patients was 57.1 years. Forty-six patients (67.6%) suffered from polytrauma. The mean thoracic AIS of the victims was calculated as 2.85 (SD = 0.76). Rib fracture was the most common chest injury, noted in 56 patients (82.4%). Pulmonary contusion was the next most frequent injury, occurring in 12 patients (17.7%). Ten patients with severe chest trauma were admitted to ICU. The median ICU stay was 11.7 (SD = 8.5) days. Five patients required intubation and ventilation, one patient was treated with noninvasive positive pressure ventilation (NPPV), and four patients were treated with high-flow nasal cannula (HFNC). Three patients died during hospitalization. The hospital mortality was 4.41%.
Chest trauma was a common type of injury after tornado. The most frequent thoracic injuries were rib fractures and pulmonary contusion. Severe chest trauma is usually associated with a high incidence of respiratory support requirements and a long length of stay in the ICU. Early initiation of appropriate oxygen therapy was vital to restoring normal respiratory function and saving lives. Going forward, HFNC might be an effective and well-tolerated therapeutic addition to the management of acute respiratory failure in chest trauma.
The aim of this study is to characterize the injury profiles and outcomes of victims of a tornado in Jiangsu Province, China.
This study retrospectively investigated the clinical records of 144 patients treated at a teaching hospital due to a tornado. Each patient’s demographic data, diagnosis, injury types, causes of injury, infection status, and outcomes were all reviewed.
Of the 144 patients, 64 (44.4%) were male, and 80 (55.6%) were female. The patients’ ages ranged from 2 months to 94 years; 91 (63.19%) were admitted within the first 12 h after the disaster. The most frequently injured sites were the body surfaces (24.48%), followed by the limbs and pelvis (21.79%) and chest (20.3%). Soft-tissue injuries and fractures were the most frequent injuries. Traumatic brain injuries were the main causes of death. Tornado-related injuries were primarily caused by flying/falling bricks, wood, and glass. Twenty-three (15.9%) patients suffered from infections, which consisted mainly of skin/soft tissue infections and pneumonia.
Destructive tornadoes often cause heavy casualties with little warning. Medical aid agencies must be prepared to accommodate the massive numbers of injured patients after a catastrophe. Proper triage and prompt treatment of injured victims may decrease mortality. (Disaster Med Public Health Preparedness. 2019;xx:xxx-xxx).
Introduction: To investigate the effects of paroxetine (PAR) on motor and cognitive function recovery in patients with non-depressed ischemic stroke (nD-AIS).
Methods: One hundred sixty-seven patients hospitalized for non-depressed acute ischemic stroke were selected and divided into treatment (T) and control (C) groups using a random number table. All patients received conventional secondary ischemic stroke prevention and rehabilitation training; patients in Group T additionally received treatment with PAR (10 mg/day during week 1 and 20 mg/day thereafter) for 3 months. The follow-up observation lasted 6 months. The Fugl–Meyer motor scale (FMMS), Montreal cognitive assessment (MoCA), and Hamilton depression scale (HAMD) were used on D0, D15, D90, and D180 (T0, 1, 2, and 3, respectively; D180 = 90 days after treatment cessation) after study initiation, and scores were compared between the groups.
Results: The FMMS and MoCA scores differed significantly between Groups T and C at T2 and T3 (p < .05); by contrast, these scores did not differ significantly between the groups at T1 (p > .05). Furthermore, the HAMD scores differed significantly between the two groups at T3 (p < .05), but not at T1 and T2 (p > .05).
Conclusions: PAR treatment may improve motor and cognitive function recovery in patients with nD-AIS. Moreover, PAR may reduce the occurrence of depression after stroke.
Ethanolamine (Etn) contained in milk is the base constituent of phosphatidylethanolamine and is required for the proliferation of intestinal epithelial cells and bacteria, which is important for maintenance of the gut microbiome and intestinal development. The present study investigated the effect of Etn on intestinal function and microbiome using 21-d-old Sprague–Dawley rats treated with 0, 250, 500 and 1000 μm Etn in drinking water for 2 weeks immediately after weaning. Growth performance, intestinal morphology, antioxidant capacity and mucosal immunity, as well as gut microbiota community composition, were evaluated. Metagenomic prediction and metabolic phenotype analysis based on 16S RNA sequencing were also carried out to assess changes in metabolic functions. We found that weaned rats administered 500 μm Etn enhanced mucosal antioxidant capacity, as evidenced by higher superoxide dismutase and glutathione peroxidase levels in the jejunum (P<0·05) compared with those in the control group. Predominant microbes including Bacteroidetes, Proteobacteria, Elusimicrobia and Tenericutes were altered by different levels of Etn compared with the control group. An Etn concentration of 500 µm shifted colonic microbial metabolic functions that are in favour of lipid- and sugar-related metabolism and biosynthesis. Etn also altered the metabolic phenotypes such as anaerobic microbial counts, and oxidative stress tolerance at over 250 µm. This is the first report for a role of Etn in modifying gut microbiota and intestinal functions. Our findings highlighted the important role of Etn in shaping gut microbial community and promotes intestinal functions, which may provide a better insight of breast-feeding to infant’s gut health.
Colistin, a peptide antibiotic belonging to the polymyxin family, is one of the last effective drugs for the treatment of multidrug resistant Gram-negative infections. Recent discovery of a novel mobile colistin resistance gene, mcr-1, from people and food animals has caused a significant public health concern and drawn worldwide attention. Extensive usage of colistin in food animals has been proposed as a major driving force for the emergence and transmission of mcr-1; thus, there is a worldwide trend to limit colistin usage in animal production. However, despite lack of colistin usage in food animals in the USA, mcr-1-positive Escherichia coli isolates were still isolated from swine. In this paper, we provided an overview of colistin usage and epidemiology of mcr-1 in food animals, and summarized the current status of mechanistic and evolutionary studies of the plasmid-mediated colistin resistance. Based on published information, we further discussed several non-colistin usage risk factors that may contribute to the persistence, transmission, and emergence of colistin resistance in an animal production system. Filling the knowledge gaps identified in this review is critical for risk assessment and risk management of colistin resistance, which will facilitate proactive and effective strategies to mitigate colistin resistance in future animal production systems.
We study a quasilinear degenerately elliptic system involving the operator curl. The leading-order term of the associated energy functional is a q-power of curl of the unknowns. It is interesting to us that the structure of the lower-order terms will play an important role in both the existence and regularity of the solutions. When the lower-order part of the energy functional is convex we obtain weak solutions by minimizing the functional in some suitable spaces of vector fields. When it is concave we obtain critical points of the truncated functional, which are weak solutions of a nonlinear eigenvalue problem. We also examine the interior Hölder regularity of the weak solutions, which indicates that the weak solution is composed of a ‘good’ divergence-free part and a ‘bad’ part in gradient form. The analysis involves local higher integrability and local Hölder gradient estimates for a translated q′-Laplace equation and a translated quasilinear equation with p-growth.
We examined the in vitro developmental competence of parthenogenetic activation (PA) oocytes activated by an electric pulse (EP) and treated with various concentrations of AZD5438 for 4 h. Treatment with 10 µM AZD5438 for 4 h significantly improved the blastocyst formation rate of PA oocytes in comparison with 0, 20, or 50 µM AZD5438 treatment (46.4% vs. 34.5%, 32.3%, and 24.0%, respectively; P < 0.05). The blastocyst formation rate was higher in the group treated with AZD5438 for 4 h than in the groups treated with AZD5438 for 2 or 6 h (42.8% vs. 38.6% and 37.2%, respectively; P > 0.05). Furthermore, 66.67% of blastocysts derived from these AZD5438-treated PA oocytes had a diploid karyotype. The blastocyst formation rate of PA and somatic cell nuclear transfer (SCNT) embryos was similar between oocytes activated by an EP and treated with 2 mM 6-dimethylaminopurine for 4 h and those activated by an EP and treated with 10 µM AZD5438 for 4 h (11.11% vs. 13.40%, P > 0.05). In addition, the level of maturation-promoting factor (MPF) was significantly decreased in oocytes activated by an EP and treated with 10 µM AZD5438 for 4 h. Finally, the mRNA expression levels of apoptosis-related genes (Bax and Bcl-2) and pluripotency-related genes (Oct4, Nanog, and Sox2) were checked by RT-PCR; however, there were no differences between the AZD5438-treated and non-treated control groups. Our results demonstrate that porcine oocyte activation via an EP in combination with AZD5438 treatment can lead to a high blastocyst formation rate in PA and SCNT experiments.