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This study aimed to demonstrate the utilization value of 1PN embryos. The 1PN zygotes collected from December 2021 to September 2022 were included in this study. The embryo development, the pronuclear characteristics, and the genetic constitutions were investigated. The overall blastocyst formation and good-quality blastocyst rates in 1PN zygotes were 22.94 and 16.24%, significantly lower than those of 2PN zygotes (63.25 and 50.23%, respectively, P = 0.000). The pronuclear characteristics were found to be correlated with the developmental potential. When comparing 1PN zygotes that developed into blastocysts to those that arrested, the former exhibited a significantly larger area (749.49 ± 142.77 vs. 634.00 ± 119.05, P = 0.000), a longer diameter of pronuclear (29.81 ± 3.08 vs. 27.30 ± 3.00, P = 0.000), and a greater number of nucleolar precursor body (NPB) (11.56 ± 3.84 vs. 7.19 ± 2.73, P = 0.000). Among the tested embryos, the diploidy euploidy rate was significantly higher in blastocysts in comparison with the arrested embryos (66.67 vs. 11.76%, P = 0.000), which was also significantly higher in IVF-1PN blastocysts than in ICSI-1PN blastocysts (75.44 vs. 25.00%, P = 0.001). However, the pronuclear characteristics were not found to be linked to the chromosomal ploidy once they formed blastocysts.
In summary, while the developmental potential of 1PN zygotes is reduced, our study shows that, in addition to the reported pronuclear area and diameter, the number of NPB is also associated with their developmental potential. The 1PN blastocysts exhibit a high diploidy euploidy rate, are recommend to be clinically used post genetic testing, especially for patients who do not have other 2PN embryos available.
Major psychiatric disorders (MPDs) are delineated by distinct clinical features. However, overlapping symptoms and transdiagnostic effectiveness of medications have challenged the traditional diagnostic categorisation. We investigate if there are shared and illness-specific disruptions in the regional functional efficiency (RFE) of the brain across these disorders.
Methods
We included 364 participants (118 schizophrenia [SCZ], 80 bipolar disorder [BD], 91 major depressive disorder [MDD], and 75 healthy controls [HCs]). Resting-state fMRI was used to caclulate the RFE based on the static amplitude of low-frequency fluctuation, regional homogeneity, and degree centrality and corresponding dynamic measures indicating variability over time. We used principal component analysis to obtain static and dynamic RFE values. We conducted functional and genetic annotation and enrichment analysis based on abnormal RFE profiles.
Results
SCZ showed higher static RFE in the cortico-striatal regions and excessive variability in the cortico-limbic regions. SCZ and MDD shared lower static RFE with higher dynamic RFE in sensorimotor regions than BD and HCs. We observed association between static RFE abnormalities with reward and sensorimotor functions and dynamic RFE abnormalities with sensorimotor functions. Differential spatial expression of genes related to glutamatergic synapse and calcium/cAMP signaling was more likely in the regions with aberrant RFE.
Conclusions
SCZ shares more regions with disrupted functional integrity, especially in sensorimotor regions, with MDD rather than BD. The neural patterns of these transdiagnostic changes appear to be potentially driven by gene expression variations relating to glutamatergic synapses and calcium/cAMP signaling. The aberrant sensorimotor, cortico-striatal, and cortico-limbic integrity may collectively underlie neurobiological mechanisms of MPDs.
Human alveolar echinococcosis is a hard-to-treat and largely untreated parasitic disease with high associated health care costs. The current antiparasitic treatment for alveolar echinococcosis relies exclusively on albendazole, which does not act parasiticidally and can induce severe adverse effects. Alternative, and most importantly, improved treatment options are urgently required. A drug repurposing strategy identified the approved antimalarial pyronaridine as a promising candidate against Echinococcus multilocularis infections. Following a 30-day oral regimen (80 mg kg−1 day−1), pyronaridine achieved an excellent therapeutic outcome in a clinically relevant hepatic alveolar echinococcosis murine model, showing a significant reduction in both metacestode size (72.0%) and counts (85.2%) compared to unmedicated infected mice, which revealed significantly more potent anti-echinococcal potency than albendazole treatment at an equal dose (metacestode size: 42.3%; counts: 4.1%). The strong parasiticidal activity of pyronaridine was further confirmed by the destructive damage to metacestode tissues observed morphologically. In addition, a screening campaign combined with computational similarity searching against an approved drug library led to the identification of pirenzepine, a gastric acid-inhibiting drug, exhibiting potent parasiticidal activity against protoscoleces and in vitro cultured small cysts, which warranted further in vivo investigation as a promising anti-echinococcal lead compound. Pyronaridine has a known drug profile and a long track record of safety, and its repurposing could translate rapidly to clinical use for human patients with alveolar echinococcosis as an alternative or salvage treatment.
Depression is highly prevalent in haemodialysis patients, and diet might play an important role. Therefore, we conducted this cross-sectional study to determine the association between dietary fatty acids (FA) consumption and the prevalence of depression in maintenance haemodialysis (MHD) patients. Dietary intake was assessed using a validated FFQ between December 2021 and January 2022. The daily intake of dietary FA was categorised into three groups, and the lowest tertile was used as the reference category. Depression was assessed using the Patient Health Questionnaire-9. Logistic regression and restricted cubic spline (RCS) models were applied to assess the relationship between dietary FA intake and the prevalence of depression. As a result, after adjustment for potential confounders, a higher intake of total FA [odds ratio (OR)T3 vs. T1 = 1·59, 95 % confidence interval (CI) = 1·04, 2·46] and saturated fatty acids (SFA) (ORT3 vs. T1 = 1·83, 95 % CI = 1·19, 2·84) was associated with a higher prevalence of depressive symptoms. Significant positive linear trends were also observed (P < 0·05) except for SFA intake. Similarly, the prevalence of depression in MHD patients increased by 20% (OR = 1.20, 95% CI = 1.01–1.43) for each standard deviation increment in SFA intake. RCS analysis indicated an inverse U-shaped correlation between SFA and depression (Pnonlinear > 0·05). Additionally, the sensitivity analysis produced similar results. Furthermore, no statistically significant association was observed in the subgroup analysis with significant interaction. In conclusion, higher total dietary FA and SFA were positively associated with depressive symptoms among MHD patients. These findings inform future research exploring potential mechanism underlying the association between dietary FA and depressive symptoms in MHD patients.
The twin-jet configuration allows two different scenarios to close the screech feedback. For each jet, there is one loop involving disturbances which originate in that jet and arrive at its own receptivity point in phase (self-excitation). The other loop is associated with free-stream acoustic waves that radiate from the other jet, reinforcing the self-excited screech (cross-excitation). In this work, the role of the free-stream acoustic mode and the guided-jet mode as a closure mechanism for twin rectangular jet screech is explored by identifying eligible points of return for each path, where upstream waves propagating from such a point arrive at the receptivity location with an appropriate phase relation. Screech tones generated by these jets are found to be intermittent with an out-of-phase coupling as a dominant coupling mode. The instantaneous phase difference between the twin jets computed by the Hilbert transform suggests that a competition between out-of-phase and in-phase coupling is responsible for the intermittency. To model wave components of the screech feedback while ensuring perfect phase locking, an ensemble average of leading spectral proper orthogonal decomposition modes is obtained from several segments of large-eddy simulation data that correspond to periods of invariant phase difference between the two jets. Each mode is then extracted by retaining relevant wavenumber components produced via a streamwise Fourier transform. Spatial cross-correlation analysis of the resulting modes shows that most of the identified points of return for the cross-excitation are synchronised with the guided jet mode self-excitation, supporting that it is preferred in closing rectangular twin-jet screech coupling.
Trauma is a significant health issue that not only leads to immediate death in many cases but also causes severe complications, such as sepsis, thrombosis, haemorrhage, acute respiratory distress syndrome and traumatic brain injury, among trauma patients. Target protein identification technology is a vital technique in the field of biomedical research, enabling the study of biomolecular interactions, drug discovery and disease treatment. It plays a crucial role in identifying key protein targets associated with specific diseases or biological processes, facilitating further research, drug design and the development of treatment strategies. The application of target protein technology in biomarker detection enables the timely identification of newly emerging infections and complications in trauma patients, facilitating expeditious medical interventions and leading to reduced post-trauma mortality rates and improved patient prognoses. This review provides an overview of the current applications of target protein identification technology in trauma-related complications and provides a brief overview of the current target protein identification technology, with the aim of reducing post-trauma mortality, improving diagnostic efficiency and prognostic outcomes for patients.
The comorbidity between schizophrenia (SCZ) and inflammatory bowel disease (IBD) observed in epidemiological studies is partially attributed to genetic overlap, but the magnitude of shared genetic components and the causality relationship between them remains unclear.
Methods
By leveraging large-scale genome-wide association study (GWAS) summary statistics for SCZ, IBD, ulcerative colitis (UC), and Crohn's disease (CD), we conducted a comprehensive genetic pleiotropic analysis to uncover shared loci, genes, or biological processes between SCZ and each of IBD, UC, and CD, independently. Univariable and multivariable Mendelian randomization (MR) analyses were applied to assess the causality across these two disorders.
Results
SCZ genetically correlated with IBD (rg = 0.14, p = 3.65 × 10−9), UC (rg = 0.15, p = 4.88 × 10−8), and CD (rg = 0.12, p = 2.27 × 10−6), all surpassed the Bonferroni correction. Cross-trait meta-analysis identified 64, 52, and 66 significantly independent loci associated with SCZ and IBD, UC, and CD, respectively. Follow-up gene-based analysis found 11 novel pleiotropic genes (KAT5, RABEP1, ELP5, CSNK1G1, etc) in all joint phenotypes. Co-expression and pathway enrichment analysis illustrated those novel genes were mainly involved in core immune-related signal transduction and cerebral disorder-related pathways. In univariable MR, genetic predisposition to SCZ was associated with an increased risk of IBD (OR 1.11, 95% CI 1.07–1.15, p = 1.85 × 10−6). Multivariable MR indicated a causal effect of genetic liability to SCZ on IBD risk independent of Actinobacteria (OR 1.11, 95% CI 1.06–1.16, p = 1.34 × 10−6) or BMI (OR 1.11, 95% CI 1.04–1.18, p = 1.84 × 10−3).
Conclusions
We confirmed a shared genetic basis, pleiotropic loci/genes, and causal relationship between SCZ and IBD, providing novel insights into the biological mechanism and therapeutic targets underlying these two disorders.
A new type of environmental chamber for X-ray diffraction was designed that could sustain elevated, internal pressures of nitrogen or any other gas under oxygen-free conditions and that allowed the positions of the specimen and edge aperture to be adjusted by remote control. It was used to determine the values of the interlayer spacing, λ, of nontronite from Garfield, Washington, in different stages of reduction at different values of Π, the swelling pressure of the nontronite. At equilibrium, Π was equal to the pressure under which water was expressed from the clay. Both partially and fully expanded layers were found to exist in the reduced nontronite, the fraction of partially expanded layers increasing with increasing Π and Fe2+/Fe3+, the ratio of Fe2+ to Fe3+ in octahedral sites. Also, λ for the partially expanded layers was found to depend on Fe2+/Fe3+ but not on Π, and λ for the fully expanded layers was found to depend on Π but not on Fe2+/Fe3+. These findings were interpreted to mean that the reduction of Fe affected the short-range interlayer forces, but not the long-range ones.
Shewanella putrefaciens is a species of metal-reducing bacteria with a versatile respiratory metabolism. This study reports that S. putrefaciens strain MR-1 rapidly reduces Fe(III) within smectite clay minerals. Up to 15% of the structural Fe within ferruginous smectite (sample SWa-1, Source Clays Repository of the Clay Minerals Society) was reduced by MR-1 in 4 h, and a range of 25% to 41% of structural Fe was reduced after 6 to 12 d during culture. Conditions for which smectite reduction was optimal, that is, pH 5 to 6, at 25 to 37 °C, are consistent with an enzymatic process and not with simple chemical reduction. Smectite reduction required viable cells, and was coupled to energy generation and carbon metabolism for MR-1 cultures with smectite added as the sole electron acceptor. Iron(III) reduction catalyzed by MR-1 was inhibited under aerobic conditions, and under anaerobic conditions it was inhibited by the addition of nitrate as an alternate electron acceptor or by the metabolic inhibitors tetrachlorosali-cylanilide (TCS) or quinacrine hydrochloride. Genetic mutants of MR-1 deficient in anaerobic respiration reduced significantly less structural Fe than wild-type cells. In a minimal medium with formate or lactate as the electron donor, more than three times the amount of smectite was reduced over no-carbon controls. These data point to at least one mechanism that may be responsible for the microbial reduction of clay minerals within soils, namely, anaerobic respiration, and indicate that pure cultures of MR-1 provide an effective model system for soil scientists and mineralogists interested in clay reduction. Given the ubiquitous distribution and versatile metabolism of MR-1, these studies may have further implications for bioremediation and water quality in soils and sediments.
Reduction of structural Fe in Na-exchanged dioctahedral smectites decreases swellability in water, but because clay interlayers also collapse in the process the concomitant effect on surface hydration energy is uncertain. This study examined the hydration behavior of oxidized and reduced dioctahedral smectite clays exchanged with polar (Na) and weakly-polar (organic) cations to determine the nature of the surface before and after Fe reduction, and to determine if clay surfaces are hydrophilic or hydrophobic. The H2O content in various dioctahedral smectites decreased if Na was replaced by tetramethylammonium (TMA), trimethylphenylammonium (TMPA), or hexadecyltrimethylammonium (HDTMA). Among the organo-clays, H2O adsorption decreased with increasing complexity of the cation. For oxidized smectites, those exchanged with TMPA retained less H2O than those exchanged with Na at all pressures. The extent of this difference depended on the clay and decreased with increasing applied pressure. Reduction of Fe(III) to Fe(II) in the octahedral sheets decreased the swelling of Na-saturated smectites, apparently causing some previously swelling interlayers to collapse. If the Na interlayer cation was exchanged to alkylammonium after reduction, but prior to swelling-pressure measurements, the swelling increased or remained near constant, suggesting that the organo-cation disrupted the collapse process of the interlayers associated with the reduced smectite layers. Reduced TMPA-saturated smectite surfaces are more strongly hydrated if the octahedral sheet is reduced than if oxidized. Thus, reduction of structural Fe increases the hydration energy of smectite basal surfaces, but swellability could decrease or increase depending on the extent of interlayer collapse occurring with different exchangeable cations.
The oxidation state of structural Fe greatly alters surface chemistry, which may have a large influence on clay-organic interactions. The effect of structural-iron oxidation state on chlorinated hydrocarbons at the clay-water interface was examined. Pentachloroethane (5CA) was reacted with oxidized, reduced, and reoxidized forms of three different smectites: montmorillonite, ferruginous smectite, and nontronite in aqueous suspension under controlled-atmosphere conditions. Pentachloroethane was found to adsorb at different rates for the three smectites. A series of 5CA-adsorption rate constants in the presence of these clays showed a strong correlation with the Fe(II) content of the clay (r2 = 0.98). The clay surface behaves as a Brønsted base and promotes 5CA dehydrochlorination. The adsorption kinetics at the clay-water interface were described by the formation of a precursor complex prior to 5CA dehydrochlorination.
Suspensions were produced by mixing Na-saturated, Upton montmorillonite with aqueous solutions containing different concentrations of 1,4-dioxane. Each suspension was deposited on a porous ceramic filter in an environmental chamber, and the solution was expressed from it by admitting gaseous helium to the chamber at a slightly elevated pressure. The chamber was fitted 1) with beryllium windows so that X-rays could be transmitted into and out of it and 2) with a drain so that the expressed solution could be conducted to the outside atmosphere. Once a filter cake had formed on the filter, the pressure of the gaseous helium was raised in successive increments and, after each increment, the c-axis layer spacing(s) was determined by X-ray diffraction. Increasing the concentration of 1,4-dioxane caused some of the fully expanded layers to collapse to the partially expanded state (c-axis spacing = 15 Å) and appeared to cause the remaining fully expanded layers to move farther apart, especially at the higher pressures. Alternative explanations were given for these apparently contradictory results.
In order to provide a theoretical foundation for the utilization of tailings as supplementary cementitious materials, the pozzolanic activity of muscovite—a typical mineral phase in tailings—before and after mechanical activation was investigated. In this study, significant pozzolanic activity of muscovite was obtained as a result of the structural and morphological changes that were induced by mechanical activation. The activated muscovite that was obtained after mechanical activation for 160 min satisfies the requirements for use as an active supplementary cementitious material, and the main characteristics of the pozzolana were as follows: median particle size (D50) of 11.7 μm, BET specific surface area of 28.82 m2 g−1, relative crystallinity of 14.99%, and pozzolanic activity index of 94.36%. Continuous grinding led to a gradual reduction in the relative crystallinity and an increase in the pozzolanic activity index due to the dehydroxylation reaction induced by mechanical activation, which occurred despite the fact that the specific surface area showed a decreasing trend when the grinding time was prolonged. Mechanically activated muscovite exhibited the capacity to react with calcium hydroxide to form calcium silicate hydrate, which is a typical characteristic of pozzolana. This experimental study provided a theoretical basis for evaluating the pozzolanic activity of muscovite using mechanical activation.
Chlorite is one of the most common Fe-bearing minerals and is susceptible to weathering in loess and soils. The conventional method for analyzing chlorite, based on XRD with the Rietveld technique, is quantitative, but very time consuming and expensive. In this paper we develop a new methodology based on diffuse reflectance spectroscopy (DRS) and selective chemical extractions to identify chlorite qualitatively in the Chinese loess sequence and present evidence suggesting that DRS may be used to quantify chlorite content. The spectral signature of chlorite in loess is obscured by Fe oxides, but becomes obvious when they are removed. Changes in the ferrous absorption band near 1140 nm vary consistently with changing chlorite content. Using this spectral feature, DRS can distinguish chlorite contents as small as 1 wt.% in loess sediments. Future possibilities for this method in other soil and sediment types need to be explored.
Oxidation-reduction processes within natural systems greatly influence the properties of sediments, soils and clays. The objective of this experimental study was to gather new evidence for the effects of changes in redox conditions (reduction and reoxidation) on structural properties of ferruginous smectite and to understand better the mechanisms involved. The <2 µm fraction of a ferruginous smectite (sample SWa-1), which contains 17.3 wt.% of total structural Fe, was studied by infrared (IR) spectroscopy. The pure Na-saturated clay was reduced by Na dithionite for 10 to 240 min to obtain various Fe(II):(total Fe) ratios ranging from 0 to 1.0. Selected reduced samples were then reoxidized completely by bubbling O2 gas through the suspensions for up to 12 h. Infrared spectra of the initially unaltered, reduced and reduced-reoxidized samples were collected. Reduction generated changes in the three studied spectral regions (O-H stretching, M-O-H deformation, and Si-O stretching), indicating that major modifications occurred within the clay crystal beyond merely a change in Fe oxidation state. partial dehydroxylation and redistribution of Fe, and perhaps Al, cations occurred upon reduction of SWa-1, changing the structural properties of its tetrahedral and octahedral sheets. Water molecules, probably generated by dehydroxylation within the octahedral sheet upon reduction, were tightly bound to the clay surface and were possibly trapped within the clay structure. Except for dehydroxylation and the Fe oxidation state, all these modifications were largely irreversible. The tightly bound water was not completely removed upon reoxidation and the cationic rearrangements generated during reduction were not reversed: either they were preserved as in the reduced state or cations were redistributed into a different configuration from the unreduced clay.
Radio frequency (RF) breakdown can result in pulse shortening and seriously degrade the stability and reliability of relativistic backward wave oscillators (RBWOs). This paper discusses the energy range of electrons causing breakdown traces in slow-wave structures (SWSs) through particle-in-cell (PIC) simulation, numerical calculation, and experimental verification. The PIC simulation and numerical calculation results reveal that the energy of the majority of the field-induced electrons bombarding the SWS surfaces after being accelerated is less than 120 keV. Furthermore, the micro appearances of the breakdown traces in SWSs and the witness targets bombarded directly by electrons of various energy levels have been analyzed. Scanning electron microscope (SEM) shows that the breakdown traces are featured with corrugated morphologies with a wide range and a shallow depth. A mass of craters emerge in the vicinity of the corrugated morphologies. These appearances are quite similar to destructive traces impacted directly by low-energy electrons (around 160 keV). Thus, it is confirmed that the breakdown traces result from the bombardment of low-energy electrons. Therefore, the breakdown mechanism of field-emitted electrons impacting on the structure surfaces in RBWOs has been further improved.
Human cystic echinococcosis (CE) is a zoonotic disorder triggered by the larval stage of Echinococcus granulosus (E. granulosus) and predominantly occurred in the liver and lungs. The M2 macrophage level is considerably elevated among the liver of patients with hepatic CE and performs an integral function in liver fibrosis. However, the mechanism of CE inducing polarisation of macrophage to an M2 phenotype is unknown. In this study, macrophage was treated with E. granulosus cyst fluid (EgCF) to explore the mechanism of macrophage polarisation. Consequently, the expression of the M2 macrophage and production of anti-inflammatory cytokines increased after 48 h treatment by EgCF. In addition, EgCF promoted polarisation of macrophage to an M2 phenotype by inhibiting the expression of transcriptional factor hypoxia-inducible factor 1-alpha (HIF-1α), which increased the expression of glycolysis-associated genes, including hexokinase 2 (HK2) and pyruvate kinase 2 (PKM2). The HIF-1α agonist ML228 also inhibited the induction of macrophage to an M2 phenotype by EgCF in vitro. Our findings indicate that E. granulosus inhibits glycolysis by suppressing the expression of HIF-1α.
Metabolic-associated fatty liver disease (MAFLD) has been proposed to replace the term non-alcoholic fatty liver disease (NAFLD) in 2020. The association between micronutrients and MAFLD has not been reported. Therefore, this study aims to explore the association between micronutrients intake and MAFLD. This was a cross-section study based on the National Health and Nutrition Examination Survey (NHANES). The dietary intake of copper, zinc, iron, and selenium was evaluated using the 24-h dietary recall interview. Logistic regression analysis was used to explore the association between micronutrients and MAFLD, and the results were shown as odds ratio (OR) with 95 % confidence intervals (CIs). A total of 5976 participants were finally included for analysis, with 3437 participants in the MAFLD group. After adjusting potential confounders, copper intake at quartile Q3 (OR = 0⋅68, 95 % CI 0⋅50, 0⋅93) and Q4 (OR = 0⋅60, 95 % CI 0⋅45, 0⋅80) was found to be associated with lower odds of MAFLD. Iron intake at Q2 (OR = 0⋅64, 95 % CI 0⋅45, 0⋅92) and Q3 (OR = 0⋅61, 95 % CI 0⋅41, 0⋅91) was associated with the lower odds of MAFLD. Our findings found that high intake of copper and adequate intake of iron were associated with MAFLD, which may provide guidance for the management of MAFLD.
Aging plays a crucial role in the mechanisms of the impacts of genetic and environmental factors on blood pressure and serum lipids. However, to our knowledge, how the influence of genetic and environmental factors on the correlation between blood pressure and serum lipids changes with age remains to be determined. In this study, data from the Chinese National Twin Registry (CNTR) were used. Resting blood pressure, including systolic and diastolic blood pressure (SBP and DBP), and fasting serum lipids, including total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C) and triglycerides (TGs) were measured in 2378 participants (1189 twin pairs). Univariate and bivariate structural equation models examined the genetic and environmental influences on blood pressure and serum lipids among three age groups. All phenotypes showed moderate to high heritability (0.37–0.59) and moderate unique environmental variance (0.30–0.44). The heritability of all phenotypes showed a decreasing trend with age. Among all phenotypes, SBP and DBP showed a significant monotonic decreasing trend. For phenotype-phenotype pairs, the phenotypic correlation (Rph) of each pair ranged from −0.04 to 0.23, and the additive genetic correlation (Ra) ranged from 0.00 to 0.36. For TC&SBP, TC&DBP, TG&SBP and TGs&DBP, both the Rph and Ra declined with age, and the Ra difference between the young group and the older adult group is statistically significant (p < .05). The unique environmental correlation (Re) of each pair did not follow any pattern with age and remained relatively stable with age. In summary, we observed that the heritability of blood pressure was affected by age. Moreover, blood pressure and serum lipids shared common genetic backgrounds, and age had an impact on the phenotypic correlation and genetic correlations.