Search

Abstract Background Genetic disorders often manifest as abnormal fetal or childhood development. Copy number variations (CNVs) represent a significant genetic mechanism underlying such disorders. Despite their importance, the effectiveness of clinical exome sequencing (CES) in detecting CNVs, particularly small ones, remains incompletely understood. We aimed to evaluate the detection of both large and small CNVs using CES in a substantial clinical cohort, including parent–offspring trios and proband only analysis. Methods We conducted a retrospective analysis of CES data from 2428 families, collected from 2018 to 2021. Detected CNV were categorized as large or small, and various validation techniques including chromosome microarray (CMA), Multiplex ligation-dependent probe amplification assay (MLPA), and/or PCR-based methods, were employed for cross-validation. Results Our CNV discovery pipeline identified 171 CNV events in 154 cases, resulting in an overall detection rate of 6.3%. Validation was performed on 113 CNVs from 103 cases to assess CES reliability. The overall concordance rate between CES and other validation methods was 88.49% (100/113). Specifically, CES demonstrated complete consistency in detecting large CNV. However, for small CNVs, consistency rates were 81.08% (30/37) for deletions and 73.91% (17/23) for duplications. Conclusion CES demonstrated high sensitivity and reliability in CNV detection. It emerges as an economical and dependable option for the clinical CNV detection in cases of developmental abnormalities, especially fetal structural abnormalities.

Background Periodontal ligament cells (PDLCs) are a major component of the periodontal ligament and have an important role in the regeneration of periodontal tissue and maintenance of homeostasis. High glucose can affect the activity and function of PDLCs in a variety of ways; therefore, it is particularly important to find ways to alleviate the effects of high glucose on PDLCs. Annexin A2 (ANXA2) is a calcium- and phospholipid-binding protein involved in a variety of cellular functions and processes, including cellular cytokinesis, cytophagy, migration, and proliferation. Aim The aim of this study was to exploring whether ANXA2 attenuates the deleterious effects of high glucose on PDLCs and promotes osteogenic differentiation capacity. Methods and results Osteogenic differentiation potential, cellular senescence, oxidative stress, and cellular autophagy were detected. Culturing PDLCs with medium containing different glucose concentrations (CTRL, 8 mM, 10 mM, 25 mM, and 40 mM) revealed that high glucose decreased the protein expression of ANXA2 (p

Metal–organic frameworks (MOFs), a new class of porous organic–organic hybrid materials controlled by self-assembly of metal atoms and organic pillars, are attracting considerable interest because of their specific properties. More recently, the advantages of different types of nanoscale metal–organic frameworks for the use of MOF nanoparticles in stomatology have been reported in the literature. This article covers the treatment of oral cancer, surface modification of implants, antibacterial dressings, and treatment of periodontitis and periodontal regeneration. It presents recent applications, future challenges, and prospects for MOFs in stomatology in four areas. It provides an overview of recent advances in the design and application of MOFs in stomatology from their intrinsic properties to different syntheses and their use as smart drug delivery systems or a combination of these.

Cotton is an important economic crop; therefore, enhancing cotton yield and cultivating superior varieties are key research priorities. The seedling stage, a critical phase in cotton production, significantly influences the subsequent growth and yield of the crop. Therefore, breeding experts often choose to measure phenotypic parameters during this period to make breeding decisions. Traditional methods of phenotypic parameter measurement require manual processes, which are not only tedious and inefficient but can also damage the plants. To effectively, rapidly, and accurately extract three-dimensional phenotypic parameters of cotton seedlings, precise segmentation of phenotypic organs must first be achieved. This paper proposes a neural network-based segmentation algorithm for cotton seedling organs, which, compared to the average precision of 75.4% in traditional unsupervised learning, achieves an average precision of 96.67%, demonstrating excellent segmentation performance. The segmented leaf and stem point clouds are used for the calculation of phenotypic parameters such as stem length, leaf length, leaf width, and leaf area. Comparisons with actual measurements yield coefficients of determination R2 of 91.97%, 90.97%, 92.72%, and 95.44%, respectively. The results indicate that the algorithm proposed in this paper can achieve precise segmentation of stem and leaf organs, and can efficiently and accurately extract three-dimensional phenotypic structural information of cotton seedlings. In summary, this study not only made significant progress in the precise segmentation of cotton seedling organs and the extraction of three-dimensional phenotypic structural information, but the algorithm also demonstrates strong applicability to different varieties of cotton seedlings. This provides new perspectives and methods for plant researchers and breeding experts, contributing to the advancement of the plant phenotypic computation field and bringing new breakthroughs and opportunities to the field of plant science research.

In this work, two approaches of forward design neural network and reverse design neural network were proposed to accelerate the design of passivation-layer structured amorphous indium gallium zinc oxide thin-film transistor (a-IGZO TFT). It was based on a neural network with the back-propagation neural network (BPNN) and general regression neural network (GRNN) as general approximators. The forward design neural network utilized the density-of-states (DOS) key parameters of a-IGZO film as input signals, and could quickly predict characteristic curves with high accuracy. The forward design effectively improved the problem of complex input/output layer parameters in the existing methods, which was significant for the prediction and optimization of a-IGZO TFT device performance. And the reverse design neural network adopts the DOS key parameters of a-IGZO film as the output signal to achieve the rapid prediction of DOS parameters of a-IGZO film. The inverse design effectively compensated the drawback that a-IGZO TFT required artificial tuning of DOS key parameters to achieve characteristic curve fitting. All in all, the neural network model can effectively determine whether the output parameters of the network meet the design objectives and whether the output parameters need to be changed by adjusting the input parameters to eventually achieve the performance prediction and material parameters optimization of a-IGZO TFT.

Abstract Head and neck squamous cell carcinoma (HNSCC) is a highly heterogeneous malignancy with poor prognosis. This article aims to explore the clinical significance of cell differentiation trajectory in HNSCC, identify different molecular subtypes by consensus clustering analysis, and develop a prognostic risk model on the basis of differentiation-related genes (DRGs) for predicting the prognosis of HNSCC patients. Firstly, cell trajectory analysis was performed on single-cell RNA sequencing (scRNA-seq) data, four molecular subtypes were identified from bulk RNA-seq data, and the molecular subtypes were predictive of patient survival, clinical features, immune infiltration status, and expression of immune checkpoint genes (ICGs)s. Secondly, we developed a 10-DRG signature for predicting the prognosis of HNSCC patients by using weighted correlation network analysis (WGCNA), differential expression analysis, univariate Cox regression analysis, and multivariate Cox regression analysis. Then, a nomogram integrating the risk assessment model and clinical features can successfully predict prognosis with favorable predictive performance and superior accuracy. We projected the response to immunotherapy and the sensitivity of commonly used antitumor drugs between the different groups. Finally, we used the quantitative Reverse Transcription-Polymerase Chain Reaction (qRT-PCR) analysis and western blot to verify the signature. In conclusion, we identified distinct molecular subtypes by cell differentiation trajectory and constructed a novel signature based on differentially expressed prognostic DRGs, which could predict the prognosis and response to immunotherapy for patients and may provide valuable clinical applications in the treatment of HNSCC.

Objective: Kruppel-associated box (KRAB) proteins reportedly play a dual role in neoplastic transformation. At present, little is known about the function of the proteins encoded by the human pogo transposable element derived with KRAB domain (POGK) gene. Herein, we evaluated the prognostic significance of POGK expression in patients with hepatocellular carcinoma (HCC). Methods: The data of HCC patients was downloaded from The Cancer Genome Atlas (TCGA) database. To determine the relationship between POGK and clinical features, logistic regression was applied. Cox regression and Kaplan-Meier analyses were used to evaluate the correlation between POGK and survival rates. Gene ontology (GO) analysis and Gene set enrichment analysis (GSEA) were conducted to identify the enriched pathways and functions associated with POGK. Results: A total of 374 HCC patients were identified in TCGA. POGK was significantly upregulated in HCC and correlated with tumor status (p = 0.036), race (p = 0.025), weight (p = 0.002), body mass index (p = 0.033), histologic grade (p < 0.001), and alpha-fetoprotein (p < 0.001). High POGK expression in HCC patients correlated with a poor outcome in terms of overall survival (p = 0.0018), progression-free survival (p = 0.0087), relapse-free survival (p = 0.045), and disease-specific survival (p = 0.014), according to Kaplan-Meier analysis. Receiver operating characteristic curve analysis showed that the area under the curve of POGK expression for HCC diagnosis was 0.891. GSEA showed that high POGK expression might activate mitotic prometaphase, kinesins, homologous DNA pairing and strand exchange, MET activates PTK2 signaling pathway, G1 to S cell cycle control, Aurora B pathway, ncRNAs involved in WNT signaling pathway, hepatitis C, and ncRNAs involved in the STAT3 signaling pathway. POGK expression correlated with the abundance of adaptive and innate immunocytes in HCC. Conclusion: High expression of POGK has high diagnostic and prognostic values in patients with HCC. Moreover, POGK expression is correlated with immune infiltration in HCC.

Abstract PandaX-4T is a ton-scale dark matter direct detection experiment using a dual-phase TPC technique at the China Jinping Underground Laboratory. Various ultra-low background technologies have been developed and applied to material screening for PandaX-4T, including HPGe gamma spectroscopy, ICP-MS, NAA, radon emanation measurement system, krypton assay station, and alpha detection system. Low background materials were selected to assemble the detector. Surface treatment procedures were investigated to further suppress radioactive background. Combining measured results and Monte Carlo simulation, the total material background rates of PandaX-4T in the energy region of 1–25 keVee are estimated to be (9.9 ± 1.9) × 10 −3 mDRU for electron recoil and (2.8 ± 0.6) × 10 −4 mDRU for nuclear recoil. In addition, natKr in the detector is estimated to be < 8 ppt.

Background: Prenatal diagnosis of fetal short long bones (SLBs) was reported to be associated with skeletal dysplasias, chromosomal abnormalities, and genetic syndromes. This study aims to identify the genetic causes for fetal short long bones, and retrospectively evaluate the additional diagnostic yield of exome sequencing (ES) for short long bones following the use of conventional genetic testing.Methods: A cohort of ninety-four fetuses with sonographically identified short long bones was analyzed by trio-exome sequencing between January 2016 and June 2021. Fetuses with abnormal results of karyotype or chromosomal microarray analysis were excluded. Variants were interpreted based on ACMG/AMP guidelines. All diagnostic de novo variants were validated by Sanger sequencing.Results: Of the 94 fetuses, 38 (40.4%) were found to carry causal genetic variants (pathogenic or likely pathogenic) in sixteen genes with 38 variants. Five fetuses (5.3%) had variant(s) of uncertain significance. Thirty-five cases (37.2%) were diagnosed as genetic skeletal dysplasias including 14 different diseases that were classified into 10 groups according to the Nosology and Classification of Genetic Skeletal Disorders. The most common disease in the cohort was achondroplasia (28.9%), followed by osteogenesis imperfecta (18.4%), thanatophoric dysplasia (10.5%), chondrogenesis (7.9%), and 3-M syndrome (5.3%). The diagnostic yield in fetuses with isolated short long bones was lower than the fetuses with non-isolated short long bones, but not reached statistical significance (27.3% vs. 44.4%; p = 0.151). Whereas, the rate in the fetuses with other skeletal abnormalities was significantly higher than those with non-skeletal abnormalities (59.4% vs. 32.5%, p = 0.023), and the diagnostic rate was significantly higher in femur length (FL) below -4SDs group compared with FL 2-4SDs below GA group (72.5% vs. 16.7%; p < 0.001). A long-term follow-up showed that outcomes for fetuses with FL 2-4SDs below GA were significantly better than those with FL below -4SDs. Additionally, fourteen (36.8%) novel short long bones-related variants were identified in the present study.Conclusion: The findings suggest that in fetuses with short long bones routine genetic tests failed to determine the underlying causes, exome sequencing could add clinically relevant information that could assist the clinical management of pregnancies. Novel pathogenic variants identified may broaden the mutation spectrum for the disorders and contributes to clinical consultation and subsequent pregnancy examination.

We present the constraints on the axial-vector and pseudo-scalar mediated WIMP-nucleus interactions from the PandaX-4T experiment, using the data set corresponding to a total exposure of 0.63 tonne⋅year. No significant signal excess is observed, and the most stringent constraints to date on the mediator mass are set for the axial-vector and pseudo-scalar simplified models. The maximum excluded mass of an axial-vector mediator is 825 GeV/c2 and that of a pseudo-scalar mediator is 106 GeV/c2. In addition, the upper limits on the spin-dependent WIMP-nucleon scattering cross-section for conventional neutron-only and proton-only interactions are derived.

In the two-component Majorana dark matter model, one dark matter particle can scatter off the target nuclei, and turn into a slightly heavier component. In the framework of a simplified model with a vector boson mediator, both the tree-level and loop-level processes contribute to the signal in direct detection experiment. In this paper, we report the search results for such dark matter from PandaX-II experiment, using total data of the full 100.7 tonne⋅day exposure. No significant excess is observed, so strong constraints on the combined parameter space of mediator mass and dark matter mass are derived. With the complementary search results from collider experiments, a large range of parameter space can be excluded.

Aurantiochytrium sp. has received much attention as a potential resource for mass production of omega-3 fatty acids, which contribute to improved growth and reproduction in aquatic animals. In this study, we evaluated the gonadal index changes in zebrafish supplemented with 1–3% Aurantiochytrium sp. crude extract (TE) and the effects of ex vivo environmental Aurantiochytrium sp. on oocytes. 1% TE group showed significant improvement in the gonadal index, and both in vitro incubation and intraperitoneal injection promoted the maturation of zebrafish oocytes. In contrast, the transcriptome revealed 576 genes that were differentially expressed between the 1% TE group and the control group, including 456 up-regulated genes and 120 down-regulated genes. Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) pathway analysis of differentially expressed genes indicated that Aurantiochytrium sp. potentially affects pathways such as lipid metabolism, immune regulation, and oocyte development in zebrafish. The results of this study enriched the knowledge of Aurantiochytrium sp. in regulating gonadal development in zebrafish and provided a theoretical basis for its application in aquaculture.

Abstract Background We presented two cases of mosaic trisomy 2 with high risk of maternal serum screening and non-invasive prenatal testing (NIPT). The invasive amniocentesis was performed and genetic tests including karyotype, single nucleotide polymorphism array(SNP-array), interphase fluorescence in situ hybridization (FISH) were employed to detect the chromosomal abnormality. Results Cytogentic analysis of the case 1 and 2 showed a mosaic karyotype consisting of two cell lines (mos 47,XY,+2[8]/46,XY[19] and mos 47,XX,+2[7]/46,XX[28], respectively). SNP-array using DNA extracted from uncultured amniotic fluid cells revealed a result of arr[GRCh38](2)x2~3, which indicated that chromosome 2 may be trisomy of mosaicism in both two cases. The results of interphases FISH confirmation test showed that three red signals of the CEP 2 specific probe in 14%(14/100) and 12%(12/100) of the two cases’ cells, respectively, which indicated a mosaicism for trisomy 2 in the uncultured amniocytes. Fetal ultrasound of case 1 suggested that the long bone is smaller than the gestational age, while the case 2 showed that the biparietal diameter (BPD), head circumference (HC) and femur length (FL) were smaller than gestational age along with abnormal cardiac structure. Conclusions We presented two cases with mosaic trisomy 2 and performed confirmatory genetic testing using cultured and uncultured amniocytes. When maternal serum screening and NIPT suggesting high risk, genetic counselor should be alert for increasing possibility of chromosomal anomalies if combined with abnormal ultrasound findings.

Abstract Background Complete clearance of intracellular viruses depends on effector cells of innate and adaptive immune systems. This study aimed to identify the relationships among antiviral cytokines produced by natural killer (NK) and T cells and clinical-virological characteristics in untreated chronic hepatitis B (CHB) patients. Methods We measured antiviral cytokines interferon-gamma (IFN-γ), tumor necrosis factor-alpha (TNF-α), and interleukin-2 (IL-2) produced by T, NK and natural killer T (NKT) cells, respectively, in a cohort with chronic hepatitis B virus (HBV) infection (CHB). We also correlated these cytokines with clinical-virological characteristics using a linear regression model. Results levels of IFN-γ+ and TNF-α+ CD4+ and CD8+ T cells were significantly higher in immune active (IA) phase than in other phases. Immune tolerant (IT) patients showed the lowest expression of IFN-γ by NK and NKT cells, and TNF-α by NK cells. IFN-γ+, TNF-α+ and IL-2+ CD4+ and CD8+ T cells frequencies were similar between IA and gray zone (GZ) phases. Principal component analysis based on cytokines confirmed that most IT patients significantly differed from inactive carriers (IC) and IA patients, while GZ patients were widely scattered. Multivariate analysis showed both T and NK cells producing IFN-γ and TNF-α, but not IL-2, had significant association with serum alanine aminotransferase (ALT). Moreover, IFN-γ+ NKT cells were associated with HBV DNA, while IFN-γ+ CD4+ and CD8+ T cells were correlated with age. Conclusion HBV clinical phases are characterized by distinct cytokine signatures, which showed relationship to viral features in these untreated CHB patients.

Background: National immunization schedules in many countries recommend HPV vaccination for females until the age of 26 years, and thus substantial numbers with reproductive age may be exposed to HPV vaccines. Objective: To assess whether inadvertent HPV vaccine exposures in the periconceptional period or during pregnancy were associated with increased risks for adverse pregnancy outcomes. Search strategy: A search of PubMed, Cochrane Library, China National Knowledge Infrastructure (CNKI), and WanFang databases (until March 31, 2019) was performed. Selection criteria: Studies that assess the risk of adverse pregnancy outcomes in HPV vaccine exposed/unexposed pregnancies were included. The adverse pregnancy outcomes included spontaneous abortion, stillbirth, small for sestational age, preterm birth, and birth defects. Data collection and analysis: The pooled relative risk (RR) was applied for the effect measure of the study. RRs and 95% confidence interval (CI) were measured when the paper did not report the effect. Heterogeneity between studies was assessed using the Cochrane’s Q and I2 statistics. Main results: Of 374 identified citations, 8 met inclusion criteria. Compared with the unexposed pregnancies, HPV vaccine exposed pregnancies were associated with no higher risk for spontaneous abortion (RR, 0.99 [95% CI, 0.90 to 1.08]); stillbirth (RR, 1.16 [95% CI, 0.71 to 1.90]); small for gestational age (RR, 0.96 [95% CI, 0.86 to 1.07]); preterm birth (RR, 1.04 [95% CI, 0.91 to 1.18]); or birth defects (RR, 1.18 [95% CI, 0.97 to 1.43]). Conclusions: Inadvertent bivalent/quadrivalent HPV vaccination during pregnancy was not associated with significantly greater risks of adverse pregnancy outcomes.

BackgroundNon-tumor tissue has a significant impact on the prognosis of head and neck squamous cell carcinoma (HNSCC). Previous studies for HNSCC have mainly focused on tumor tissue, greatly neglecting the role of non-tumor tissue. This study aimed to identify HNSCC subtypes and prognostic gene sets based on activity changes of immunologic and hallmark gene sets in tumor and adjacent non-tumor tissues to improve patient prognosis.MethodsIn the study, we used gene set variation analysis (GSVA) to estimate the relative enrichment of gene sets over the sample population, and identified relevant subtypes of HNSCC by Cox regression analysis and the non-negative matrix factorization (NMF) method. The representative gene sets were identified by calculating the differential enrichment score of gene sets between each of the two subgroups, intersecting them, and screening them using univariate Cox regression analysis. The least absolute shrinkage and selection operator (LASSO) regression analysis was used to screen out potential prognostic gene sets and establish a risk model. Finally, genes encompassed in each prognostic gene set were obtained and subjected to enrichment analysis and protein–protein interaction (PPI) in tumor and non-tumor tissues.ResultsWe identified three subtypes of HNSCC based on gene sets in tumor and non-tumor tissues, and patients with subtype 1 had a higher survival rate than subtypes 2 and 3. The subtypes were related to the survival status, pathological stage, and T stage of HNSCC patients. In total 450 differentially gene sets and 39 representative gene sets were obtained by calculating the differential enrichment score of gene sets between each of the two subgroups, intersecting them, and screening them using univariate Cox regression analysis. The prognostic model was constructed by LASSO regression analysis, including five prognostic gene sets. Kaplan-Meier analysis indicated that different risk groups and the five prognostic gene sets were associated with survival status in the model. Finally, enrichment analysis and PPI indicated that non-tumor and tumor tissues affect the prognosis of HNSCC patients in different ways.ConclusionIn conclusion, we provide a novel insight for rational treatment strategies and precise prognostic assessments based on tumor and adjacent non-tumor tissues, suggesting that more emphasis should be placed on changes in adjacent non-tumor and tumor tissues, rather than just the tumor itself.

Precise measurement of two-neutrino double beta decay (DBD) half-life is an important step for the searches of Majorana neutrinos with neutrinoless double beta decay. We report the measurement of DBD half-life of 136Xe using the PandaX-4T dual-phase Time Projection Chamber (TPC) with 3.7-tonne natural xenon and the first 94.9-day physics data release. The background model in the fiducial volume is well constrained in situ by events in the outer active region. With a 136Xe exposure of 15.5 kg-year, we establish the half-life as 2.27±0.03stat.±0.10syst.×1021 years. This is the first DBD half-life measurement with natural xenon and demonstrates the physics capability of a large-scale liquid xenon TPC in the field of rare event searches.

Feed is one of the most important external signals in fish that stimulates its feeding behavior and growth. The intake of feed is the main factor determining efficiency and cost, maximizing production efficiency in a fish farming firm. The physiological mechanism regulating food intake lies between an intricate connection linking central and peripheral signals that are unified in the hypothalamus consequently responding to the release of appetite-regulating genes that eventually induce or hinder appetite, such as apelin; a recently discovered peptide produced by several tissues with diverse physiological actions mediated by its receptor, such as feed regulation. Extrinsic factors have a great influence on food intake and feeding behavior in fish. Under these factors, feeding in fish is decontrolled and the appetite indicators in the brain do not function appropriately thus, in controlling conditions which result in the fluctuations in the expression of these appetite-relating genes, which in turn decrease food consumption. Here, we examine the research advancements in fish feeding behavior regarding dietary selection and preference and identify some key external influences on feed intake and feeding behavior. Also, we present summaries of the results of research findings on apelin as an appetite-regulating hormone in fish. We also identified gaps in knowledge and directions for future research to fully ascertain the functional importance of apelin in fish.

The marine protist Aurantiochytrium produces several bioactive chemicals, including EPA (eicosapentaenoic acid), DHA (docosahexaenoic acid), and other critical fish fatty acids. It has the potential to improve growth and fatty acid profiles in aquatic taxa. This study evaluated zebrafish growth performance in response to diets containing 1% to 3% Aurantiochytrium sp. crude extract (TE) and single extract for 56 days. Growth performance was best in the 1% TE group, and therefore, this concentration was used for further analyses of the influence of Aurantiochytrium sp. Levels of hepatic lipase, glucose-6-phosphate dehydrogenase, acetyl-CoA oxidase, glutathione peroxidase, and superoxide dismutase increased significantly in response to 1% TE, while malic enzyme activity, carnitine lipid acylase, acetyl-CoA carboxylase, fatty acid synthase, and malondialdehyde levels decreased. These findings suggest that Aurantiochytrium sp. extract can modulate lipase activity, improve lipid synthesis, and decrease oxidative damage caused by lipid peroxidation. Transcriptome analysis revealed 310 genes that were differentially expressed between the 1% TE group and the control group, including 185 up-regulated genes and 125 down-regulated genes. Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) pathway analyses of the differentially expressed genes revealed that Aurantiochytrium sp. extracts may influence liver metabolism, cell proliferation, motility, and signal transduction in zebrafish.

The long-term prognosis of a fetus with cardiac rhabdomyoma (CR) depends on the correlation with tuberous sclerosis complex (TSC). In recent years, the numerous variations of uncertain significance (VUS) of TSC genes produced by high-throughput sequencing have made counseling challenging, studies until now have tended to side-step the tricky topics. Here, we integrated detailed parental phenotype, echocardiography, neuro MRI, and genetic information to conduct a comprehensive evaluation of 61 CR fetuses. As a result, multiple CRs and cerebral lesions appeared in 90 and 80%, respectively of fetuses with pathogenic (P)/likely pathogenic (LP) TSC1/TSC2 variations. Overall, 85.7% of the live-born infants with P/LP presented with TSC-associated signs. While, 85.7% of VUS without nervous findings had good prognoses. Genetic evidence and cerebral MRI findings are the most sensitive index to assess long-term prognosis, which complement and confirm each other for a TSC diagnosis. In total, 68.9% of fetuses with CR could benefit from this multidisciplinary approach, which turned out to be potentially clinically actionable with precise clinical/genetic diagnosis or had a foreseeable outcome. Our practice provides a practical and feasible solution for perinatal management and prognostic guidance for fetuses with CR.

PACS1 neurodevelopmental disorder (PACS1-NDD) is a category of rare disorder characterized by intellectual disability, speech delay, dysmorphic facial features, and developmental delay. Other various physical abnormalities of PACS1-NDD might involve all organs and systems. Notably, there were only two unique missense mutations [c.607C > T (p.Arg203Trp) and c.608G > A (p.Arg203Gln)] in PACS1 that had been identified as pathogenic variants for PACS1-NDD or Schuurs-Hoeijmakers syndrome (SHMS). Previous reports suggested that these common missense variants were likely to act through dominant-negative or gain-of-function effects manner. It is still uncertain whether the intragenic deletion or duplication in PACS1 will be disease-causing. By using whole-exome sequencing, we first identified a novel heterozygous multi-exon deletion covering exons 12–24 in PACS1 (NM_018026) in four individuals (two brothers and their father and grandfather) in a three-generation family. The younger brother was referred to our center prenatally and was evaluated before and after the birth. Unlike SHMS, no typical dysmorphic facial features, intellectual problems, and structural brain anomalies were observed among these four individuals. The brothers showed a mild hypermyotonia of their extremities at the age of 3 months old and recovered over time. Mild speech and cognitive delay were also noticed in the two brothers at the age of 13 and 27 months old, respectively. However, their father and grandfather showed normal language and cognitive competence. This study might supplement the spectrum of PACS1-NDD and demonstrates that the loss of function variation in PACS1 displays no contributions to the typical SHMS which is caused by the recurrent c.607C > T (p.Arg203Trp) variant.

Abstract Background Hearing loss is a prevalent sensorineural disorder and a major public health issue in China. It is suggested that half of all cases of hearing loss can be prevented through public health measures. However, national strategies for hearing healthcare are not implemented well in Guangdong and some other regions in China. Methods To develop a community-based service model for the prevention and control of hearing loss in Guangdong, we integrated the model with multiple maternal and child healthcare models, and set up a series of clinical programs along with an optimum timeline for the preventive measures and intervention treatments to take place. A total of 36,090 families were enrolled in the study, including 358 high-risk families and 35,732 general-risk families. Results The study lasted for 6.5 years, and 30,769 children were born during that period. A total of 42 children were born with congenital deafness; 17 of them were born into families with advanced genetic risks for hearing loss, 9 were born with specific medical conditions, and 16 were born into general-risk families. About one third of them were diagnosed prenatally, others were diagnosed within 3 months of age, and 72% of them received interventions initiated before 6 months of age. 13 children presented with delayed hearing loss; 9 of them were diagnosed with delayed hereditary sensorineural deafness in neonatal period, and 4 were diagnosed within 3 months after onset. Timely interventions were provided to them, with appropriate referrals and follow-ups. Beside these, 80 families were identified with genetic susceptibility to aminoglycoside ototoxicity. Detailed medication guides were provided to prevent aminoglycoside-induced hearing loss. Moreover, through health education and risk reduction strategies, the prevalence of TORCH syndrome decreased from 10.7 to 5.2 per 10,000. Additionaly, the awareness rates of health knowledge about hearing healthcare significantly increased in the cohort. Conclusions Adapting national strategies for local or district projects could be an important step in implementing hearing loss prevention measures, and developing community-based service models could be of importance in carrying them out.

Abstract Background Hepatitis B virus (HBV) replicates non-cytopathically in the hepatocytes and HBV-related diseases are caused by immune-mediated inflammatory events. This study aimed to identify the relationship between clinical-virological characteristics and immunity in untreated chronic hepatitis B (CHB) patients. Methods A total of 209 CHB patients were categorized into immune tolerant (IT, n = 17), inactive carrier (IC, n = 20), immune active (IA, n = 120), and gray zone (GZ, n = 72) phases. The quantitative hepatitis B surface antigen (qHBsAg), hepatitis B e antigen (HBeAg), anti-HBeAg (HBeAb), HBV genotype, viral mutant and frequencies of interleukin (IL)-4, IL-17, IL-10 and interferon-gamma (IFN-γ) produced by CD4+ and CD8+ T cells were tested. We also correlated these cytokines with clinical-virological characteristics using a linear regression model. Results CD8+ T cells frequency were significantly decreased in IT patients. Levels of CD4+ T cells IL-4+ or IL-10+ were strongly negatively associated with qHBsAg titers. The frequency of IFN-γ produced by CD4+ and CD8+ T cells showed significant positive association with age and alanine aminotransferase (ALT) level, while that had negative association with qHBsAg titers. Additionally, the ratios of mutations in the HBV precore (PC) stop codon and basal core promoter (BCP) and the combined mutations were 32.5, 27.2, and 11.3%, respectively. The frequency of CD4+ T cells IL-17+ was higher in patients with a PC mutation than that in patients carrying a wild-type sequence. Finally, little associations among T cell derived IL-4, IL-10, IL-17, and IFN-γ was observed in the current untreated CHB cohort. Conclusions Several components of the immune system were correlated with HBV factors that influence an inflammatory process during CHB. Of particular relevance are the significant associations of between CD4+ T cells IL-4+ and qHBsAg level, and between CD4+ T cells IL-17+ and the presence of a mutation in PC.

Abstract Background Prader-Willi syndrome (PWS) and Angelman syndrome (AS) are clinically distinct neurodevelopmental disorders caused by absence of paternally or maternally expressed imprinted genes on chromosome 15q11.2-q13.3 region. Methods 3331 individuals was recruited from June 2013 to December 2016 under an institutional review board-approved protocol of informed consent. The methylation-specific PCR was employed as a first-tier screening test. The multiplex-fluorescent-labeled STR linkage analysis was carried out to define the underlying genetic mechanisms. The chromosomal microarray analysis was employed to identify chromosomal breakpoints in confirmed cases, and to detect other chromosomal abnormalities in undiagnosed cases. Genetic counseling and recurrence risk assessment were provided to families with affected individuals. Results The methylation-specific PCR identified 36 PWS suspected patients and 13 AS suspected patients. UBE3A sequence analysis identified another 1 patient with AS. The STR linkage analysis define the underlying genetic mechanisms. Thirty PWS patients were with paternal deletions on chromosome region 15q11-q13, 5 with isodisomic uniparental disomy and 1 with mixed segmental isodisomic/ heterodisomic uniparental disomy of maternal chromosome 15. Twelve AS patients were with maternal deletions, 1 with isodisomic uniparental disomy and 1 with UBE3A gene mutation. The chromosomal microarray analysis identified chromosomal breakpoints in confirmed cases, and detected chromosomal abnormalities in another 4 patients with clinically overlapped features but tested negative for PWS/AS. Genetic counseling was offered to all families with affected individuals. Conclusions Identifying the disorders at early age, establishing the molecular mechanisms, carrying out treatment intervention and close monitoring can significantly improve the prognosis of PWS/AS patients.

This study investigated whether antibody-modified immunomagnetic microspheres (IMs) can be used to detect and quantify circulating tumor cells (CTCs) originating from gliomas in liquid biopsies and whether CTC counts in clinical samples are related to the degree of malignancy of gliomas based on clinical data. Epidermal growth factor receptor (EGFR)-antibody-modified and epithelial cell adhesion molecule (EpCAM)-modified IMs were developed, their physical properties, including particle size and zeta potential as well as their biocompatibility, were characterized, and their ability to detect CTCs originating from gliomas was evaluated using a mouse xenograft model and clinical specimens [cerebrospinal fluid (CSF) and peripheral blood collected from 30 patients with gliomas]. The results showed that EGFR-IMs and EpCAM-IMs had low cytotoxicity and that they could capture CTCs in mouse and human biofluids with high capture efficiency. Moreover, CTC counts in the human CSF were positively correlated with glioma grade. Thus, EGFR-IMs and EpCAM-IMs have clinical applicability for the diagnosis of glioma and for monitoring treatment response in patients.

In recent years, with the rapid development of the construction industry, the demand for natural river sand has become increasingly prominent. Development of alternatives to river sand has become an interesting direction for concrete research. In this paper, coal gangue was proposed to replace part of the river sand to produce coal gangue fine aggregate concrete, while waste polyethene terephthalate (PET) bottles were used as raw materials to make PET fibers to improve the mechanical properties of coal gangue fine aggregate concrete. There were two parts of the test conducted. In the first part, the compressive strength of the gangue fine aggregate concrete cube, splitting tensile strength, axial compressive strength, and static elastic modulus were studied when the substitution rate of coal gangue increased from 0% to 50%. Referring to the equation of the full stress-strain curve of plain concrete, the stress-strain constitutive equation of coal gangue fine aggregate concrete was analyzed and studied. By comparing with plain concrete, it was found that the coal gangue concrete with a replacement rate of 50% had higher compressive strength and tensile strength, but its brittleness was significantly greater than that of plain concrete in the later stage. In the second part, by studying the effect of different PET fiber content on the mechanical properties of coal gangue fine aggregate concrete with a replacement rate of 50%, it was found that when the addition of PET fiber was 0.1% and 0.3%, not only were compressive strength, splitting tensile strength, static elastic modulus, and flexural strength of the gangue fine aggregate concrete effectively improved but also the brittleness of concrete can be significantly reduced. The study found that after adding 0.3% PET fiber, the coal gangue fine aggregate concrete with a replacement rate of 50% has better mechanical properties and less brittleness.

Doping of rare-earth ions in a host is one of the important strategies to modify the microstructure and electrical and optical properties. This work demonstrated the significant improvement of luminescence and photocatalytic performances of Bi7O5F11 via Eu3+ doping. Bi7O5F11 has a typical Sillén–Aurivillius structure, which shows an intrinsic luminescence band peaked at 527 nm with a decay time of 0.041 µs. The intrinsic emission quenches in Bi7O5F11:Eu3+, which shows characteristic transitions from 5D0,1,2,3 levels to 7FJ (J = 0–4) ground states. An experimental red-LED lamp was successfully fabricated by encapsulating Bi7O5F11:Eu3+ with a transparent resin. Bi7O5F11 has poor photocatalytic ability, which just can happen under UV light irradiation. The fast decay time (0.041 µs) of Bi7O5F11 causes an efficient recombination of the light-induced charges, resulting in a lower photocatalytic effect. Bi7O5F11:Eu3+ shows the improved photocatalytic abilities compared with pure Bi7O5F11. 4f levels of Eu3+ provide a longer decay time (1 ms) for the excited states of Bi7O5F11, which prevents the recombination of the light-induced charges. Importantly, Eu3+ doping moves the required wavelength in photocatalytic reactions from UV light (pure Bi7O5F11) to visible wavelength in Bi7O5F11:Eu3+. Bi7O5F11:Eu3+ could be further investigated to develop a multifunctional bismuth material such as dielectric, photoelectric, and photochemical abilities.

Abstract Background MiRNAs are involved in aberrant DNA methylation through regulation of DNA methyltransferases (DNMTs) in the pathogenesis and progression of glioblastomas (GBM). MiR-152-3p was down-expressed in human malignancies, and served as a tumor suppressor. Neurofibromatosis type 2 (NF2) was significantly decreased in GBM tissues with a high level of methylation. However, the link between miR-152-3p, DNMT1 and methylation of NF2 in GBM is not clearly established. This study was conducted to detect the mechanism between miR-152-3p, DNMT1 and NF2 in GBM. Methods The levels of DNMT1 and NF2 expression were studied by qRT-PCR, Western blot, immunofluorescence, and immumohistochemical staining. Methylation in the promoter region of NF2 was detected by methylation-specific PCR and bisulfate genomic sequencing PCR. Cell proliferation was examined by Cell-Counting Kit-8 and 5-ethynyl-2′-deoxyuridine assay, and cell invasion was evaluated by transwell assay. Flow cytomery and Hoechst staining were used to analyze cell apoptosis. A dual luciferase system was used to confirm the relationship between miR-152-3p and DNMT1. Results Methylation of NF2 and DNMT1 was markedly increased, and miR-152-3p was downregulated in GBM tissues and glioma cells. Both knockdown of DNMT1 and overexpression miR-152-3p showed that demethylation activated the expression of NF2. Furthermore, miR-152-3p directly targeted DNMT1. Both miR-152-3p overexpression and DNMT1 knockdown significantly induced cell apoptosis and inhibited invasive activity. This was also observed after NF2 overexpression. Conclusions These results indicated that miR-152-3p can inhibit glioma cell proliferation and invasion activities by decreasing DNMT1. The restoration of miR-152-3p may have therapeutic application in the treatment of GBM.

Abstract G2 and S phase-expressed-1 (GTSE1) regulates G1/S cell cycle transition. It was recently reported to be overexpressed in certain human cancers, but its significance and mechanism(s) in hepatocellular carcinoma (HCC) remain unknown. Here, we showed preferential GTSE1 upregulation in human HCC tissues and cell lines that positively correlated with Ki67. GTSE1 knockdown by short hairpin RNA resulted in deficient colony-forming ability and depleted capabilities of HCC cells to migrate and invade. Conversely, exogenous GTSE1 overexpression enhanced colony formation and stimulated HCC cell migration and invasion. Furthermore, GTSE1 silencing was associated with the downregulation of N-cadherin, β-catenin, and Snail, whereas GTSE1 overexpression caused the opposite effects. GTSE1 upregulated Snail via both transcription and protein degradation pathways. Additionally, GTSE1 modulated the sensitivity of HCC to 5-fluorouracil therapy. High GTSE1 correlates with chemo-resistance, while low GTSE1 increases drug sensitivity. Kaplan-Meier survival analysis indicated that high GTSE1 levels were significantly associated with poor overall survival. In conclusion, high expression of GTSE1 is commonly noted in HCC and is closely correlated with migration and invasion by epithelial-to-mesenchymal transition (EMT) modulation. Activated GTSE1 significantly interferes with chemotherapy efficacy and influences the probability of survival of patients with HCC. GTSE1 may thus represent a promising molecular target.

Te4+ and V5+-codoped Bi2O3 nanoparticles were synthesized via the sol-gel method. The sample showed a loose aggregation with the ball-like nanoparticles (of 200–400 nm). X-ray powder diffraction (XRD) refinements were used to investigate the crystallinity formations. As-prepared Bi2−xTexVxO3 (x = 0.1, 0.2) samples present δ-Bi2O3 phase with space group of Fm-3m at room temperature. The results indicate that the cubic structure could be stabilized via Te4+ and V5+-codoping in Bi2O3 lattices. UV–vis absorption measurements concluded that Te4+/V5+-codoping could modify the band gap of δ-Bi2O3. Te/V-doped samples could harvest more visible light in longer-wavelength region. The improved photocatalysis of Bi2−xTexVxO3 (x = 0.1, 0.2) on RhB photodegradation was in presence with the irradiation of visible-light (λ > 420 nm). To elucidate the photocatalytic mechanisms, XPS measurements, luminescence and lifetimes and impedance spectra were measured and analyzed. The improved photocatalysis was related with the microstructure changes and the multivalent V ions. Keywords: Semiconductor, Photocatalysis, Band energy, Solar materials, Optical properties

[Objectives] To study the coating process of paeonol sustained release pills by extrusion-spheronization method taking ethyl cellulose as the coating material. [Methods] Paeonol pills were made by Âuari AW-95 Full Automatic Pill Making Machine. Coating of paeonol sustained release pills was prepared by Auari Mini Pill Polishing Machine. The prescription and process factors of paeonol sustained release pills coating were investigated by single factor experiment and orthogonal experiment. The release of paeonol sustained release pills was determined according to the cumulative release curve of paeonol. [ Results] The prepared paeonol sustained release pills released slowly within 24 h, and the release rate reached 80% in 12 h. [Conclusions] The prepared paeonol sustained release pills basically meet the 24 h sustained release standard, and can be further developed and applied. [ABSTRACT FROM AUTHOR]

Contrary to most Pr3+-doped materials, Pr3+-doped BaGd2(MoO4)4 crystals do not generate the 1320 nm photoluminescence, which is used as an amplifier for O-band optical communications. However, it is found to generate a broad emission band in the wavelength region of 1400-1550 nm with full-width at half-maximum of 130nm. Pr3+-doped BaGd2(MoO4)4 with broadband near-infrared emission is expected to be useful as an amplifier material in the E- and S-band optical communication systems. Disappearance of the 1320 nm emission in BaGd2(MoO4)4 is explained by the energy gap law with high maximum phonon energy (944 cm-1) of BaGd2(MoO4)4. The 1400-1550 nm emission has the maximum intensity at 1mol.% Pr3+ concentration. The concentration quenching is understood by cross-relaxation process. [ABSTRACT FROM AUTHOR]

Brain metastases (BMs) are the most common intracranial malignancy with poor prognosis. Patients with intracranial tumors are at greater risk for thrombotic complications and intracranial hemorrhage. Rivaroxaban is a potent oral anticoagulant with the high selectivity of direct factor Xa inhibition. The incidence and severity of rivaroxaban-triggered intratumoral hemorrhage (ITH) in patients with BMs remain unknown. A 57-year-old woman was diagnosed with multiple lung, bone, and BMs from unknown primary cancer origin, and refused any invasive procedures to confirm tumor pathology. However, this patient had a relatively favorable outcome after treating with cabozantinib, an inhibitor of multiple tyrosine kinases. The patient survived over 2 years and developed deep vein thrombosis of right lower limb. Oral rivaroxaban was prescribed, and the multifocal catastrophic ITH was encountered after 1 week. The last head computed tomography imaging revealed a rare but typical image of diffuse hemorrhagic metastases. Hemorrhagic-prone BMs, therapeutic rivaroxaban, and cabozantinib treatment increase risks to develop ITH. In this case rivaroxaban was the trigger to this terminal event. This case is a miserable lesson and keeps reminding us to stay vigilant in clinical practice even when there is a potential benefit for anticoagulation in such population. [ABSTRACT FROM AUTHOR]

Sm2+ ions doped KSrPO4 were prepared by high-temperature solid-state reaction method. The samples were investigated by x-ray powder diffraction, photoluminescence excitation and emission spectra, and luminescence decay measurements. After excitation into the 4f55d1 levels, the emission of Sm2+ ions showed 5D0→7FJ (J=0,1,2) emission together with the broad 5d→4f emission band. The luminescence of Sm2+ ions was sensitive to the temperature. With the decreasing of the temperature, the broad 5d→4f emission band of Sm2+ ions gradually quenched, while 5D0→7FJ (J=0,1,2) emission lines could be clearly detectable. Based on the luminescence properties of Sm2+ ions and structure of KSrPO4 crystal, the crystallographic sites and the energy structure correlated with 4f→5d transitions of Sm2+ ions in KSrPO4 were discussed. [ABSTRACT FROM AUTHOR]

The effect of the cationic sites on the luminescent properties of [Eu.sup.3+] in [Gd.sub.2]BaZn[O.sub.5] is examined by the site-selective laser excitation and emission spectroscopy along with luminescence decays. The [Eu.sup.3+] ions have occupied two cationic sites and the Stark energy levels of [Eu.sup.3+] at two different sites in [Gd.sub.2]BaZn[O.sub.5] are assigned from selectively excited emission spectra at 10 K.

[Sm.sup.2+]-doped [Li.sub.2]O-SrO-[B.sub.2][O.sub.3] glass sample is prepared by the conventional melt quenching method in air atmosphere and [Sm.sup.2+] ions in this borate glass are obtained by x-ray irradiation reduction method. The microstructure of Sm ions in the [Li.sub.2]-SrO-[B.sub.2][O.sub.3] glass is examined and the microstructure is helpful in understanding the reduction mechanism of [Sm.sup.2+] ion in borate glasses.

A high-temperature solid-state reaction method was used to prepare [Sm.sup.2+] ions doped KSrP[O.sub.4] and its crystal structure was analyzed by x-ray diffraction (XRD). The crystallographic sites and the energy structure were found to be associated with 4f->5d transitions of [Sm.sup.2+] ions in KSrP[O.sub.4].

An investigation on the upconversion emission properties of [Nd.sup.3+] ions doped in PbWO4 crystal is conducted by pulsed laser excitation into the [super 4]F5/2+[super 2]G(1)7/2 levels at temperatures from 10 to 295 K. Several upconversion blue emissions from the [super 2]P1/2 level and the absorption lines due to the [super 4]I9/2->[super 2]P1/2 transition indicate multisite structure of the [Nd.sup.3+] ions in the PbWO4 lattices.

Aims: A large number of studies have suggested that exportins (XPOs) play a pivotal role in human cancers. In the present study, we analyzed XPO mRNA expression in cancer tissues and explored their prognostic value in hepatocellular carcinoma (HCC). Methods: Transcriptional and survival data related to XPO expression in HCC patients were obtained through the ONCOMINE and UALCAN databases. Survival analysis plots were drawn with Gene Expression Profiling Interactive Analysis (GEPIA). Sequence alteration data for XPOs were obtained from The Cancer Genome Atlas (TCGA) database and c-BioPortal. Gene functional enrichment analyses were performed with Database for Annotation, Visualization and Integrated Discovery (DAVID). Results: Compared with normal liver tissues, significant XPO mRNA overexpression was observed in HCC cancer tissues. There was a trend of higher XPO expression in more advanced clinical stages and lower differentiated pathological grades of HCC. In HCC patients, high expression of XPO1, CSE1L, XPOT, XPO4/5/6 was related to poor overall survival (OS), and XPO1, CSE1L and XPO5/6 were correlated with poor disease-free survival (DFS). The main genetic alterations in XPOs involved mRNA up-regulation, DNA amplification and deletion. General XPO mutations were remarkably associated with worse OS and mostly affected the pathways of RNA transport and oocyte meiosis. Conclusion: High expression of XPOs was associated with a poor prognosis in HCC patients. XPOs may be exploited as good prognostic biomarkers for survival in HCC patients. [ABSTRACT FROM AUTHOR]

Trophinin-associated protein (TROAP) was a protein first identified to mediate the process of embryo transplantation and later found to be involved in microtubule regulation. However, little is known about the role of TROAP in hepatocellular carcinoma (HCC). In the present study, we reported that both TROAP mRNA and protein expressions were downregulated in human HCC samples as well as cell lines. A high level of TROAP was associated with small tumor size (p < 0.05), minor tumor nodules (p < 0.01), and mild vein invasion (p < 0.05). We further constructed in vitro TROAP depletion and overexpression HCC cell models. TROAP depletion significantly enhanced the proliferation and colony formation abilities, whereas TROAP overexpression had an inhibitory effect on the growth of HCC cells. The G1/S phase arrest by TROAP overexpression correlated with increased cell cycle inhibitors p21 and p27, and declined cell cycle promoting kinase complex CDK6/cyclin D1. Depressed TROAP expression enhanced the migration ability, while the opposite influence was observed in TROAP-overexpressed HCC cells. Taken together, these results indicate that TROAP suppresses cellular growth and migration in HCC. This discovery will further our understanding of the pathogenic mechanisms of human HCC. [ABSTRACT FROM AUTHOR]

Subpixel mapping (SPM) is a technique that produces hard classification maps at a spatial resolution finer than that of the input images produced when handling mixed pixels. Existing spatial attraction model (SAM) techniques have been proven to be an effective SPM method. The techniques mostly differ in the way in which they compute the spatial attraction, for example, from the surrounding pixels in the subpixel/pixel spatial attraction model (SPSAM), from the subpixels within the surrounding pixels in the modified SPSAM (MSPSAM), or from the subpixels within the surrounding pixels and the touching subpixels within the central pixel in the mixed spatial attraction model (MSAM). However, they have a number of common defects, such as a lack of consideration of the attraction from subpixels within the central pixel and the unequal treatment of attraction from surrounding subpixels of the same distance. In order to overcome these defects, this study proposed an improved SAM (ISAM) for SPM. ISAM estimates the attraction value of the current subpixel at the center of a moving window from all subpixels within the window, and moves the window one subpixel per step. Experimental results from both Landsat and MODIS imagery have proven that ISAM, when compared with other SAMs, can improve SPM accuracies and is a more efficient SPM technique than MSPSAM and MSAM. [ABSTRACT FROM AUTHOR]

The concentration effect on the photoluminescence (PL) of the praseodymium Pr3+ ion is studied at 298-12 K for barium gadolinium molybdate (BaGd2(MoO4)4, called BGM) crystals with a wide Pr3+ concentration range of 0.05-25.0 mol%. Three types of concentration dependences are observed for the emissions although all types show PL quenching at high concentrations. The first type (Type A) has the maximum PL intensity at about 10 mol% with a non-zero intensity at high concentrations, which is observed for the 3P0 emissions except for emission at 621 nm. The second and third types (Type B-1 and B-2) have the maximum at about 1 mol% with a finite residual intensity and nearly zero intensity at high concentrations, respectively, which are observed for the 621 nm emission and all the 1D2 emissions. It is suggested that the energy migration mechanism is responsible for Type A, while the non-resonant crossrelaxation is responsible for Type B-1 and the resonant cross-relaxation for Type B-2. [ABSTRACT FROM AUTHOR]