Alpha-asarone alleviates cutaneous hyperalgesia by inhibiting hyperexcitability and neurogenic inflammation via TLR4/NF-κB/NLRP3 signaling pathway in a female chronic migraine rat model.

Migraine is a highly prevalent neurological disorder. Alpha-asarone (ASA), a major active component found in Acorus tatarinowii, plays a crucial role in analgesia and anti-inflammation for neuropathic pain. This study aimed to assess the efficacy of ASA against migraine and elucidate its potential mechanisms using a well-established inflammatory soup (IS) migraine female rat model. Mechanical pain thresholds were assessed daily before IS infusion, followed by post-infusion administration of ASA. Subsequently, spontaneous locomotor activities, exploratory behavior, short-term spatial memory, and photophobia were blindly evaluated after the final drug administration. The rats were then sacrificed for investigation into the underlying mechanisms of action. Network pharmacology was also employed to predict potential targets and pathways of ASA against migraine. The anti-inflammatory activity of ASA and pathway-related proteins were examined in BV2 cells stimulated with lipopolysaccharides (LPS). The results demonstrated that ASA ameliorated cutaneous hyperalgesia and photophobia while improving spatial memory and increasing exploratory behavior in IS rats. ASA attenuated central sensitization-related indicators and excessive glutamate levels while enhancing GABA synthesis. ASA rescued neuronal loss in the cortex and hippocampus of IS rats. Notably, the ability of ASA to improve spatial memory performance in the Y maze test was not observed with sumatriptan, a first-line treatment drug, suggesting the potential involvement of the TLR4 pathway. Moreover, ASA suppressed microglial activation, reduced pro-inflammatory factors, and downregulated TLR4, MyD88, p-NF-κB/NF-κB, NLRP3, caspase-1, IL-1ß, and IL-18. Overall, ASA demonstrated its potential to alleviate hyperalgesia and improve behavioral performance in migraine rats by inhibiting hyperexcitability and microglia-related inflammation.

Prenatal diagnosis of 17q12 copy number variants in fetuses via chromosomal microarray analysis - A retrospective cohort study and literature review.

Purpose: 17q12 copy number variants (CNVs) have variable presentations and incomplete penetrance, challenging prenatal counseling and management. This study aims to investigate the intrauterine phenotype. Methods: We included 48 fetuses diagnosed with 17q12 microdeletion or microduplication by chromosomal microarray analysis. Results: For 17q12 deletion, renal anomalies were found in 35 fetuses (35/37, 94.6 %), with hyperechogenic kidneys (HEK, 28/37, 75.7 %) and multicystic dysplastic kidneys (17/37, 45.9 %) being the most common findings. Duodenal obstruction (DO) was most frequently combined in 17q12 duplication fetuses. In addition, cardiac abnormalities were the first reported prenatal phenotype in 17q12 duplication fetuses. Conclusion: Our study shows that HEK and DO are the most predominant presentations of 17q12 deletion and duplication, respectively, and cardiac structural abnormalities may be associated with the latter. Although 17q12 CNVs have incomplete penetrance and variable expressivity and may be mainly involved in neurodevelopmental disorders, their short-term prognosis appears positive.

State Interaction for Relativistic Four-Component Methods: Choose the Right Zeroth-Order Hamiltonian for Late-Row Elements.

We present several schemes based on the spin-separation of the Dirac-Coulomb-Breit Hamiltonian for the perturbative treatment of relativistic four-component Hamiltonians within the state interaction framework. While state interaction approaches traditionally use zeroth-order scalar-relativistic states, we develop augmented zeroth-order Hamiltonians with increasing accuracy and investigate convergence to the variational limit as a function of the choice of zeroth-order Hamiltonian. The state interaction schemes developed in this work are benchmarked using ground-state fine-structure splitting of late-row atoms and diatomic hyrides. Although the scalar-relativistic zeroth-order Hamiltonian exhibits significant errors in ground-state fine-structure splitting, the predictive accuracy can be improved by augmenting the zeroth-order Hamiltonian with one- and two-electron vector-relativistic operators (e.g., spin-orbit, spin-spin, orbit-orbit). This work lays the theoretical foundation for the development of low-scaling, high-accuracy perturbative relativistic methods suitable for late-row elements.

Association of prenatal Cleft Lip and Palate ultrasound abnormalities with copy number variants at a single Chinese tertiary center.

BACKGROUD: A systematic analysis was conducted to investigate the molecular etiology of fetal cleft lip and/or palate (CL/P) and the association between various types of CL/P and copy number variations (CNVs), as well as their impact on birth outcomes. METHODS: In this retrospective study conducted between January 2016 and July 2022, a cohort of pregnancies diagnosed with fetal CL/P was enrolled and comprehensive clinical data for all cases were extracted from our medical record database, including demographic data about the pregnancies, ultrasound findings, results of Chromosomal microarray (CMA), as well as relevant pregnant and perinatal outcomes. RESULTS: Among the 358 cases, 32 clinically significant variants in 29 (8.1%) fetuses with CL/P were detected by CMA. In 338 singleton pregnancies, the diagnostic yield of CMA in the context of CL/P fetuses was determined to be 7.7% (26/338). CP cases exhibited a relatively higher prevalence of pathogenic/likely pathogenic CNVs at a rate of 25% (3/12), followed by CLP cases at 8.0% (23/288). Notably, the CL group did not demonstrate any pathogenic/likely pathogenic CNV findings among the examined cases (0/38). The diagnostic rate of clinically significant variants was notably higher in the non-isolated CL/P group than in the isolated CL/P group (11/33, 33.3% vs. 15/305, 4.9%, p < 0.001). Within the remaining 20 twin pregnancies, three clinically significant variants (15%) were observed. CONCLUSIONS: This study provides powerful evidence supporting the efficacy of CMA as a valuable tool for facilitating the prenatal genetic diagnosis of fetal CL/P. The presence of CP and CLP in fetal cases demonstrated a relatively higher incidence of pathogenic/likely pathogenic CNVs. Moreover, when these cases were accompanied by additional ultrasound abnormalities, the likelihood of identifying diagnostic CNVs significantly increased. Conversely, cases of CL alone might not be associated with positive CNVs. The present data may significantly enhance prenatal diagnosis accuracy and facilitate informed genetic counseling for cases of fetal CL/P.

Identification of a Novel 16.8Kb Deletion of the α-Globin Gene Cluster by Third-Generation Sequencing.

α-thalassemia major (α-TM) often causes Hb Bart's (c4) hydrops fetalis and severe obstetric complications in the mother. Step-wise screening for couples at risk of having offspring(s) affected by α-TM is the efficient prevention method but some rare genotypes of thalassemia cannot be detected. A 32-year-old male with low HbA2 (2.4%) and mild anemia was performed real-time PCR-based multicolor melting curve analysis (MMCA) because his wife was -SEA deletion carrier. The result of multiplex ligation-dependent probe amplification (MLPA) suggested the existence of -SEA deletion in the proband. A novel deletion of the α-globin gene cluster was found using self-designed MLPA probes combined with longer PCR, which was further accurately described to be 16.8Kb (hg38, Chr16:1,65,236-1,82,113) deletion by the third-generation sequencing. A fragment ranging from 1,53,226 to 1,54,538(GRch38/hg38) was identified which suggested the existence of the homologous recombination event. The third-generation sequencing is accurate and efficient in obtaining accurate information for complex structural variations.

MiR-424-5p Inhibits Proliferation, Migration, Invasion and Angiogenesis of the HTR-8/SVneo Cells Through Targeting LRP6 Mediated ß-catenin.

The aim of this study was to investigate the effects of miR-424-5p on biological behaviors and angiogenesis of the HTR-8/SVneo Cells. Our study included 60 parturient women, which were divided into an PA group (placenta accreta, n = 30) and a normal group (normal placenta, n = 30). QPCR was used to measure the expression of miR-424-5p in placental tissues. The effects of the miR-424-5p mimic on proliferation, migration, and invasion of human HTR-8/SVneo cells and angiogenesis were analyzed. The potential modulated relationship between miR-424-5p and low-density lipoprotein receptor-related protein-6 (LRP6) was demonstrated by luciferase assay. The expression of LRP6, ß-catenin, matrix metalloproteinase-2 (MMP-2), placental growth factor (PGF) and vascular endothelial growth factor (VEGF) were measured by qPCR and Western blot assays. The expression of miR-424-5p in the PA group was significantly decreased than that in the normal group. The expression of miR-424-5p has negative correlation with blood loss. Upregulation of miR-424-5p significantly suppressed the cell proliferation, migration, and invasion of HTR-8/SVneo cells in vitro, as well as the tube formation of human umbilical vein endothelial cells (HUVECs). The luciferase assay demonstrated that LRP6 was a target of miR-424-5p. The expression of LRP6, ß-catenin, MMP-2, PGF and VEGF were also decreased with upregulation of miR-424-5p (p < 0.05). The inhibitory effects of miR-424-5p on HTR-8/SVneo cells and angiogenesis were enhanced by downregulation of LRP6, but were reversed by upregulation of LRP6. The present study suggests that downregulation of miR-424-5p is related to the occurrence of PA. Enhancing miR-424-5p inhibits proliferation, migration, invasion and angiogenesis of the HTR-8/SVneo cells through targeting LRP6 mediated ß-catenin, providing more insights about PA.

Microcapsule Modification Strategy Empowering Separator Multifunctionality to Enhance Safety of Lithium-Metal Batteries.

The uncontrollable growth of lithium dendrites and the flammability of electrolytes are the direct impediments to the commercial application of high-energy-density lithium metal batteries (LMBs). Herein, this study presents a novel approach that combines microencapsulation and electrospinning technologies to develop a multifunctional composite separator (P@AS) for improving the electrochemical performance and safety performance of LMBs. The P@AS separator forms a dense charcoal layer through the condensed-phase flame retardant mechanism causing the internal separator to suffocate from lack of oxygen. Furthermore, it incorporates a triple strategy promoting the uniform flow of lithium ions, facilitating the formation of a highly ion-conducting solid electrolyte interface (SEI), and encouraging flattened lithium deposition with active SiO2 seed points, considerably suppressing lithium dendrites growth. The high Coulombic efficiency of 95.27% is achieved in Li-Cu cells with additive-free carbonate electrolyte. Additionally, stable cycling performance is also maintained with a capacity retention rate of 93.56% after 300 cycles in LFP//Li cells. Importantly, utilizing P@AS separator delays the ignition of pouch batteries under continuous external heating by 138 s, causing a remarkable reduction in peak heat release rate and total heat release by 23.85% and 27.61%, respectively, substantially improving the fire safety of LMBs.

Tetravalent Cerium Alkyl and Benzyl Complexes.

High-valent cerium complexes of alkyl and benzyl ligands are unprecedented due to the incompatibility of the typically highly oxidizing Ce4+ ion and the reducing alkyl or benzyl ligand. Herein we report the synthesis and isolation of the first tetravalent cerium alkyl and benzyl complexes supported by the tri-tert-butyl imidophosphorane ligand, [NP(tBu)3]1-. The Ce4+ monoiodide complex, [Ce4+I(NP(tert-butyl)3)3] (1-CeI), serves as a precursor to the alkyl and benzyl complexes, [Ce4+(Npt)(NP(tert-butyl)3)3] (2-CeNpt) (Npt = neopentyl, CH2C(CH3)3) and [Ce4+(Bn)(NP(tert-butyl)3)3] (2-CeBn) (Bn = benzyl, CH2Ph). The bonding and structure of these complexes are characterized by single-crystal XRD, NMR and UV-vis-NIR spectroscopy, cyclic voltammetry, and DFT studies.

Single-cell RNA sequencing reveals cellular and molecular landscape of fetal cystic hygroma.

BACKGROUND: The molecular mechanism of fetal cystic hygroma (CH) is still unclear, and no study has previously reported the transcriptome changes of single cells in CH. In this study, single-cell transcriptome sequencing (scRNA-seq) was used to investigate the characteristics of cell subsets in the lesion tissues of CH patients. METHODS: Lymphoid tissue collected from CH patients and control donors for scRNA-seq analysis. Differentially expressed gene enrichment in major cell subpopulations as well as cell-cell communication were analyzed. At the same time, the expression and interactions of important VEGF signaling pathway molecules were analyzed, and potential transcription factors that could bind to KDR (VEGFR2) were predicted. RESULTS: The results of scRNA-seq showed that fibroblasts accounted for the largest proportion in the lymphatic lesions of CH patients. There was a significant increase in the proportion of lymphatic endothelial cell subsets between the cases and controls. The VEGF signaling pathway is enriched in lymphatic endothelial cells and participates in the regulation of cell-cell communication between lymphatic endothelial cells and other cells. The key regulatory gene KDR in the VEGF signaling pathway is highly expressed in CH patients and interacts with other differentially expressed EDN1, TAGLN, and CLDN5 Finally, we found that STAT1 could bind to the KDR promoter region, which may play an important role in promoting KDR up-regulation. CONCLUSION: Our comprehensive delineation of the cellular composition in tumor tissues of CH patients using single-cell RNA-sequencing identified the enrichment of lymphatic endothelial cells in CH and highlighted the activation of the VEGF signaling pathway in lymphoid endothelial cells as a potential modulator. The molecular and cellular pathogenesis of fetal cystic hygroma (CH) remains largely unknown. This study examined the distribution and gene expression signature of each cell subpopulation and the possible role of VEGF signaling in lymphatic endothelial cells in regulating the progression of CH by single-cell transcriptome sequencing. The enrichment of lymphatic endothelial cells in CH and the activation of the VEGF signaling pathway in lymphatic endothelial cells provide some clues to the pathogenesis of CH from the perspective of cell subpopulations.

Comparison of Variational and Perturbative Spin-Orbit Coupling within Two-Component CASSCF.

The modeling of spin-orbit coupling (SOC) remains a challenge in computational chemistry due to the high computational cost. With the rising popularity of spin-driven processes and f-block metals in chemistry and materials science, it is incumbent on the community to develop accurate multiconfigurational SOC methods that scale to large systems and understand the limits of different treatments of SOC. Herein, we introduce an implementation of perturbative SOC in scalar-relativistic two-component CASSCF (srX2C-CASSCF-SO). Perspectives on the limitations and accuracy of srX2C-CASSCF-SO are presented via benchmark calculations.

Prenatal diagnosis and outcomes in fetuses with duplex kidney.

OBJECTIVE: Duplex kidney is a relatively frequent form of urinary system abnormality. This study aimed to elucidate the value of chromosomal microarray analysis (CMA) and whole exome sequencing (WES) for duplex kidney and the perinatal outcomes of duplex kidney fetuses. METHODS: This retrospective cohort study included 63 patients with duplex kidney diagnosed using antenatal ultrasound between August 2013 and January 2023. We reviewed the clinical characteristics, genetic test results, and pregnancy outcomes of the patients. RESULTS: Among the 63 cases based on the inclusion criteria, the CMA detected seven (11.1%) clinically significant variants and nine variants of uncertain significance (VUS), and the pathogenic/likely pathogenic (P/LP) copy number variations (CNVs) in the recurrent region that were associated with prenatal duplex kidney included 17q12, 17p13.3, and 22q11.2. No significant disparity was observed in the CMA detection rate between the unilateral and bilateral groups, or between the isolated and non-isolated groups. WES identified three (50%) P/LP single-gene variants in six fetuses with duplex kidney. We detected the following pathogenic genes in the duplex kidney fetuses: KMT2D, SMPD4, and FANCI. Pregnancy termination in cases where clinically significant variants were detected by genetic testing was different in statistical significance from that in cases with negative results (9/10, 90.0% vs 8/48, 16.7%, P < 0.001). CONCLUSION: This study elucidated the value of CMA and WES for fetal duplex kidney, proving that CMA and WES may be useful tools in prenatal diagnosis and genetic counseling.

Association of prenatal thoracic ultrasound abnormalities with copy number variants at a single Chinese tertiary center.

OBJECTIVE: To systematically evaluate the association of prenatal thoracic ultrasound abnormalities with copy number variants (CNVs). METHODS: Chromosomal microarray (CMA) data and clinical characteristics from fetuses with thoracic ultrasound abnormalities were retrieved and analyzed. RESULTS: Thoracic ultrasound findings were mainly isolated except for fetal pleural effusion (FPE) and pulmonary hypoplasia. The diagnostic yield of CMA for thoracic anomaly was 9.66%, and FPE (17/68, 25%), pulmonary hypoplasia (1/8, 12.5%), and congenital diaphragmatic hernia (CDH) (6/79, 7.59%) indicated relatively high pathogenic/likely pathogenic (P/LP) CNV findings. The detection rate for P/LP CNVs was obviously increased in non-isolated thoracic anomalies (27.91% vs. 1.96%, P < 0.0001), non-isolated FPE (37.78% vs. 0%, P = 0.0007) and non-isolated congenital pulmonary airway malformation (CPAM) (27.27% vs. 0%, P < 0.0001), and significantly different among thoracic anomalies. Additionally, the rate of termination of pregnancy in cases with non-isolated thoracic anomalies (58.49% vs. 12.34%, P < 0.0001) and P/LP CNVs (85.71% vs. 24.15%, P < 0.0001) was obviously increased. CONCLUSION: The present study expanded phenotype spectrums for particular recurrent CNVs. FPE, CDH, and pulmonary hypoplasia indicated relatively high P/LP CNV findings among common thoracic ultrasound abnormalities, CPAM associated with other ultrasound abnormalities increased the incidence of diagnostic CNVs, while bronchopulmonary sequestration might not be associated with positive CNVs. The present data recommended CMA application for cases with prenatal thoracic ultrasound abnormalities, especially non-isolated FPE, non-isolated CPAM, CDH, and pulmonary hypoplasia.

Functional analysis of a novel splice site variant in the ASAH1 gene.

BACKGROUND: Acid ceramidase (ACDase) deficiency is an ultrarare autosomal recessive lysosomal disorder caused by pathogenic N-acylsphingosine amidohydrolase (ASAH1) variants. It presents with either Farber disease (FD) or spinal muscular atrophy with progressive myoclonic epilepsy (SMA-PME). OBJECTIVE: The study aims to identify a novel splice site variant in a hydrops fetus that causes ASAH1-related disorder, aid genetic counseling, and accurate prenatal diagnosis. METHODS: We report a case of hydrops fetalis with a novel homozygous mutation in ASAH1 inherited from non-consanguineous parents. We performed copy number variation sequencing (CNV-Seq) and whole exome sequencing (WES) on the fetus and family, respectively. Minigene splicing analyses were conducted to confirm the pathogenic variants. RESULTS: WES data revealed a splice site variant of the ASAH1 (c.458-2A>T), which was predicted to affect RNA splicing. Minigene splicing analyses found that the c.458-2A>T variant abolished the canonical splicing of intron 6, thereby activating two cryptic splicing products (c.456_458ins56bp and c.458_503del). CONCLUSIONS: Overall, we identified a novel splice site variant in the mutational spectrum of ASAH1 and its aberrant effect on splicing. These findings highlight the importance of ultrasonic manifestation and family history of fetal hydrops during ASAH1-related disorders and could also aid genetic counseling and accurate prenatal diagnosis. To the best of our knowledge, this is the shortest-lived account of ASAH1-related disorders in utero with severe hydrops fetalis.

Prenatal diagnosis of polycystic renal diseases: diagnostic yield, novel disease-causing variants, and genotype-phenotype correlations.

BACKGROUND: Polycystic renal disease is a frequent congenital anomaly of the kidneys, but research using chromosomal microarray analysis and exome sequencing in fetuses with polycystic renal disease remains sparse, with most studies focusing on the multisystem or genitourinary system. OBJECTIVE: This study aimed to assess the detection rate of detectable genetic causes of fetal polycystic renal disease at different levels, novel disease-causing variants, and genotype-phenotype correlations. STUDY DESIGN: This study included 220 fetal polycystic renal disease cases from January 2014 to June 2022. Cases were divided into the following 3 groups: isolated multicystic dysplastic kidneys, nonisolated multicystic dysplastic kidneys, and suspected polycystic kidney disease group. We reviewed data on maternal demographics, ultrasonographic results, chromosomal microarray analysis/exome sequencing results, and pregnancy outcomes. RESULTS: In our cohort, chromosomal microarray analysis identified 19 (8.6%) fetuses carrying chromosomal abnormalities, and the most common copy number variation was 17q12 microdeletion (7/220; 3.2%). Furthermore, 94 families chose to perform trio-exome sequencing testing, and 21 fetuses (22.3%) were found to harbor pathogenic/likely pathogenic variants. There was a significant difference in the live birth rate among the 3 groups (91/130 vs 46/80 vs 1/10; P<.001). Among 138 live birth cases, 106 (78.5%) underwent postnatal ultrasound review, of which 95 (89.6%) had a consistent prenatal-postnatal ultrasound diagnosis. CONCLUSION: For both isolated and nonisolated polycystic renal disease, our data showed high detection efficiency with both testing tools. The detection of novel pathogenic variants expands the known disease spectrum of polycystic renal disease-associated genes while enriching our understanding of the genotype-phenotype correlation. Therefore, we consider it feasible to perform chromosomal microarray analysis+exome sequencing testing in fetal polycystic renal disease. Moreover, prenatal-postnatal ultrasound concordance was greater, the live birth rate was higher, and prognosis was better when known genetic disorders were excluded, indicating that genetic testing results significantly influenced pregnancy decisions.

The performance of a new type accelerator uRT-linac 506c evaluated by a quality assurance automation system.

PURPOSE: The purpose of this study was to evaluate the performance of our quality assurance (QA) automation system and to evaluate the machine performance of a new type linear accelerator uRT-linac 506c within 6 months using this system. METHODS: This QA automation system consists of a hollow cylindrical phantom with 18 steel balls in the phantom surface and an analysis software to process electronic portal imaging device (EPID) measurement image data and report the results. The performance of the QA automation system was evaluated by the tests of repeatability, archivable precision, detectability of introduced errors, and the impact of set-up errors on QA results. The performance of this linac was evaluated by 31 items using this QA system over 6 months. RESULTS: This QA system was able to automatically deliver QA plan, EPID image acquisition, and automatic analysis. All images acquiring and analysis took approximately 4.6 min per energy. The preset error of 0.1 mm in multi-leaf collimator (MLC) leaf were detected as 0.12 ± 0.01 mm for Bank A and 0.10 ± 0.01 mm in Bank B. The 2 mm setup error was detected as -1.95 ± 0.01 mm, -2.02 ± 0.01 mm, 2.01 ± 0.01 mm for X, Y, Z directions, respectively. And data from the tests of repeatability and detectability of introduced errors showed the standard deviation were all within 0.1 mm and 0.1°. and data of the machine performance were all within the tolerance specified by AAPM TG-142. CONCLUSIONS: The QA automation system has high precision and good performance, and it can improve the QA efficiency. The performance of the new accelerator has also performed very well during the testing period.

Alpha-Asarone Ameliorates Neurological Dysfunction of Subarachnoid Hemorrhagic Rats in Both Acute and Recovery Phases via Regulating the CaMKII-Dependent Pathways.

Early brain injury (EBI) is the leading cause of poor prognosis for patients suffering from subarachnoid hemorrhage (SAH), particularly learning and memory deficits in the repair phase. A recent report has involved calcium/calmodulin-dependent protein kinase II (CaMKII) in the pathophysiological process underlying SAH-induced EBI. Alpha-asarone (ASA), a major compound isolated from the Chinese medicinal herb Acorus tatarinowii Schott, was proven to reduce secondary brain injury by decreasing CaMKII over-phosphorylation in rats' model of intracerebral hemorrhage in our previous report. However, the effect of ASA on SAH remains unclear, and the role of CaMKII in both acute and recovery stages of SAH needs further investigation. In this work, we first established a classic SAH rat model by endovascular perforation and intraperitoneally administrated different ASA doses (10, 20, and 40 mg/kg) 2 h after successful modeling. Then, the short- and long-term neurobehavioral performances were blindly evaluated to confirm ASA's efficacy against SAH. Subsequently, we explored ASA's therapeutic mechanism in both acute and recovery stages using histopathological examination, TUNEL staining, flow cytometry, Western-blot, double-immunofluorescence staining, and transmission electron microscopy (TEM) observation. Finally, KN93, a selective CaMKII inhibitor, was applied in oxyhemoglobin-damaged HT22 cells to explore the role of CaMKII in ASA's neuroprotective effect. The results demonstrated that ASA alleviated short- and long-term neurological dysfunction, reduced mortality and seizure rate within 24 h, and prolonged 14-day survival in SAH rats. Histopathological examination showed a reduction of neuronal damage and a restoration of the hippocampal structure after ASA treatment in both acute and recovery phases of SAH. In the acute stage, the Western-blot and flow cytometer analyses showed that ASA restored E/I balance, reduced calcium overload and CaMKII phosphorylation, and inhibited mitochondrion-involved apoptosis, thus preventing neuronal damage and apoptosis underlying EBI post-SAH. In the recovery stage, the TEM observation, double-immunofluorescence staining, and Western-blot analyses indicated that ASA increased the numbers of synapses and enhanced synaptic plasticity in the ipsilateral hippocampi, probably by promoting NR2B/CaMKII interaction and activating subsequent CREB/BDNF/TrkB signaling pathways. Furthermore, KN93 notably reversed ASA's neuroprotective effect on oxyhemoglobin-damaged HT22 cells, confirming CaMKII a potential target for ASA's efficacy against SAH. Our study confirmed for the first time that ASA ameliorated the SAH rats' neurobehavioral deterioration, possibly via modulating CaMKII-involved pathways. These findings provided a promising candidate for the clinical treatment of SAH and shed light on future drug discovery against SAH.

Machine learning-based ensemble prediction model for the gamma passing rate of VMAT-SBRT plan.

PURPOSE: The purpose of this study was to accurately predict or classify the beam GPR with an ensemble model by using machine learning for SBRT(VMAT) plans. METHODS: A total of 128 SBRT VMAT plans with 330 arc beams were retrospectively selected, and 216 radiomics and 34 plan complexity features were calculated for each arc beam. Three models for GPR prediction and classification using support vector machine algorithm were as follows: (1) plan complexity feature-based model (plan model); (2) radiomics feature-based model (radiomics model); and (3) an ensemble model combining the two models (ensemble model). The prediction performance was evaluated by calculating the mean absolute error (MAE), root mean square error (RMSE), and Spearman's correlation coefficient (SC), and the classification performance was measured by calculating the area under the receiver operating characteristic curve (AUC), accuracy, specificity, and sensitivity. RESULTS: The MAE, RMSE and SC at the 2 %/2 mm gamma criterion in the test dataset were 1.4 %, 2.57 %, and 0.563, respectively, for the plan model; 1.42 %, and 2.51 %, and 0.508, respectively, for the radiomics model; and 1.33 %, 2.49 %, and 0.611, respectively, for the ensemble model. The accuracy, specificity, sensitivity, and AUC at the 2 %/2 mm gamma criterion in the test dataset were 0.807, 0.824, 0.681, and 0.854, respectively, for the plan model; 0.860, 0.893, 0.624, and 0.877, respectively, for the radiomics model; and 0.852, 0.871, 0.710, and 0.896, respectively, for the ensemble model. CONCLUSIONS: The ensemble model can improve the prediction and classification performance for the GPR of SBRT (VMAT).

Prenatal genetic diagnosis associated with fetal ventricular septal defect: an assessment based on chromosomal microarray analysis and exome sequencing.

Objective: In the study, we investigated the genetic etiology of the ventricular septal defect (VSD) and comprehensively evaluated the diagnosis rate of prenatal chromosomal microarray analysis (CMA) and exome sequencing (ES) for VSD to provide evidence for genetic counseling. Methods: We carried out chromosomal microarray analysis (CMA) on 468 fetuses with VSD and exome sequencing (ES) on 51 fetuses. Results: In our cohort, 68 (14.5%) VSD fetuses received a genetic diagnosis, including 61 (13.03%, 61/468) cases with chromosomal abnormalities and seven (13.7%, 7/51) cases with gene sequence variants. The detection rate of total pathogenic and likely pathogenic gene variations in the non-isolated VSD group (61/335, 18.2%, 55 by QF-PCR/karyotype/CMA + 6 by ES) was significantly higher than that in the isolated VSD group (7/133, 5.3%, 6 by QF-PCR/karyotype/CMA + 1 by ES, p = 0.000). The most common copy number variation (CNV) was 22q11.2 microdeletion syndrome. Additionally, we found six previously unreported variants, which expanded the variation spectrum of VSD-related genes. Conclusion: In this study, CNVs and sequence variants were found in 13.03% and 13.7% of cases, respectively. ES can be recommended for fetuses with VSD without chromosome abnormalities and pathogenic CNVs, especially those that are combined with other ultrasound abnormalities.

Exploring Locality in Molecular Dirac-Coulomb-Breit Calculations: A Perspective.

The Dirac-Coulomb-Breit (DCB) operator is widely recognized for its ability to accurately capture relativistic effects and spin-physics in molecular calculations. However, due to its high computational cost, there is a need to develop low-scaling approximations without compromising accuracy. To tackle this challenge, it becomes essential to gain a deeper understanding of the DCB operator's behavior. This work aims to explore local integral approximations, shedding light on the locality of the parts of the charge-current distribution due to the small component. In particular, we propose an atomic Breit approximation that leverages an analysis of the behavior observed in a series of gold chains. Through benchmark studies of metal complexes, we evaluated the accuracy and performance of the proposed atomic Breit approximation. This work provides a comprehensive understanding of the behavior of the charge-current distribution in terms of its contributions from its AO basis constituents, facilitating the development of low-scaling methods that strike a balance between computational efficiency and accuracy.

Prenatal diagnosis and perinatal outcomes of twin pregnancies disharmonious for one fetus with nuchal translucency above the 95th percentile.

OBJECTIVE: To assess prenatal diagnosis and pregnancy outcomes in twin pregnancies where one fetus has nuchal translucency (NT) above the 95th percentile. METHOD: In this retrospective analysis, 130 twin pregnancies (260 fetuses) in which one twin had an NT measurement above the 95th percentile while that of the other twin was normal were analyzed. Prenatal diagnostic results such as G bands, chromosomal microarray analysis, ultrasound findings, and pregnancy outcomes were reviewed. RESULTS: Karyotype analysis and CMA results revealed that 15 (15.6 percent, 15/96) fetuses exhibited chromosomal abnormalities and that 13 fetuses were Variant of Uncertain Significance. Chromosome abnormalities were detected at a rate of 8.9% (5/56) in the DCT group and 25.0% (10/40) in the MCT group (p = 0.033, X2 = 4.571). 2 fetuses in DCT (3.9 percent, 2/51) and 4 fetuses in MCT (13.3 percent, 4/30) (p = 0.187) revealed structural abnormalities among the cases with normal prenatal diagnosis. Fetuses in the DCT group had an overall survival rate of 75.4 percent (95/126), whereas those in the MCT group had a survival rate of 60.4 percent (81/134) (p = 0.01, X2 = 6.636). According to the findings of Logistics regression analysis, NT thickening, maternal age and method of conception were all significant risk factors for chromosome abnormalities. CONCLUSION: In twin pregnancies with one fetus with NT above the 95th percentile, the prevalence of fetal structural abnormalities of the MCT group and the DCT group were comparable. Pregnant women's age and mode of pregnancy are risk factors for chromosomal abnormalities.