ABSTRACT
The Zhejiang Han population, a subgroup of the Southern Han ethnic group, resides in Zhejiang Province, situated on the southeast coast of China. In this study, we conducted HLA genotyping for 813 voluntary umbilical cord blood donors from the Zhejiang Han population, targeting 11 HLA loci, namely HLA-A, HLA-B, HLA-C, HLA-DRB1, HLA-DRB3/4/5, HLA-DQA1, HLA-DQB1, HLA-DPA1, and HLA-DPB1, using the next-generation sequencing method. Our analysis of the alleles and haplotypes revealed a high degree of polymorphism within these loci. A total of 289 unique HLA alleles were identified, with the HLA-B locus exhibiting the most significant diversity, while HLA-DRB4 displayed the lowest variation. Due to the inherent limitations of the sequencing method, some unresolvable alleles in the specific loci, such as HLA-DRB1, HLA-DPA1, and HLA-DPB1, were assigned as G group designation. In our comprehensive analysis across all 11 HLA loci, a total of 1204 haplotypes were estimated. The distribution of these alleles was similar to those of the Chinese Southern Han population while highly different from the Caucasian population. These findings contribute to a deeper understanding of the genetic characteristics of HLA loci within the Chinese Southern Han population.
ABSTRACT
Magnetic soft actuators and robots have attracted considerable attention in biomedical applications due to their speedy response, programmability, and biocompatibility. Despite recent advancements, the fabrication process of magnetic actuators and the reprogramming approach of their magnetization profiles continue to pose challenges. Here, a facile fabrication strategy is reported based on arrangements and distributions of reusable magnetic pixels on silicone substrates, allowing for various magnetic actuators with customizable architectures, arbitrary magnetization profiles, and integration of microfluidic technology. This approach enables intricate configurations with decent deformability and programmability, as well as biomimetic movements involving grasping, swimming, and wriggling in response to magnetic actuation. Moreover, microfluidic functional modules are integrated for various purposes, such as on/off valve control, curvature adjustment, fluid mixing, dynamic microfluidic architecture, and liquid delivery robot. The proposed method fulfills the requirements of low-cost, rapid, and simplified preparation of magnetic actuators, since it eliminates the need to sustain pre-defined deformations during the magnetization process or to employ laser heating or other stimulation for reprogramming the magnetization profile. Consequently, it is envisioned that magnetic actuators fabricated via pixel-assembly will have broad prospects in microfluidics and biomedical applications.
ABSTRACT
Water network rearrangement from the ligand-unbound state to the ligand-bound state is known to have significant effects on the protein-ligand binding interactions, but most of the current machine learning-based scoring functions overlook these effects. In this study, we endeavor to construct a comprehensive and realistic deep learning model by incorporating water network information into both ligand-unbound and -bound states. In particular, extended connectivity interaction features were integrated into graph representation, and graph transformer operator was employed to extract features of the ligand-unbound and -bound states. Through these efforts, we developed a water network-augmented two-state model called ECIFGraph::HM-Holo-Apo. Our new model exhibits satisfactory performance in terms of scoring, ranking, docking, screening, and reverse screening power tests on the CASF-2016 benchmark. In addition, it can achieve superior performance in large-scale docking-based virtual screening tests on the DEKOIS2.0 data set. Our study highlights that the use of a water network-augmented two-state model can be an effective strategy to bolster the robustness and applicability of machine learning-based scoring functions, particularly for targets with hydrophilic or solvent-exposed binding pockets.
Subject(s)
Proteins , Water , Ligands , Databases, Protein , Molecular Docking Simulation , Proteins/metabolism , Protein BindingABSTRACT
Improving the generalization ability of scoring functions remains a major challenge in protein-ligand binding affinity prediction. Many machine learning methods are limited by their reliance on single-modal representations, hindering a comprehensive understanding of protein-ligand interactions. We introduce a graph-neural-network-based scoring function that utilizes a triplet contrastive learning loss to improve protein-ligand representations. In this model, three-dimensional complex representations and the fusion of two-dimensional ligand and coarse-grained pocket representations converge while distancing from decoy representations in latent space. After rigorous validation on multiple external data sets, our model exhibits commendable generalization capabilities compared to those of other deep learning-based scoring functions, marking it as a promising tool in the realm of drug discovery. In the future, our training framework can be extended to other biophysical- and biochemical-related problems such as protein-protein interaction and protein mutation prediction.
Subject(s)
Drug Discovery , Machine Learning , Ligands , Mutation , Neural Networks, ComputerABSTRACT
Type V osteogenesis imperfecta (OI) is a form of OI characterized by radial head dislocation (RHD), calcification of interosseous membrane (CIM), and hyperplastic callus (HPC). In this study, we characterized the clinical features of 28 type V OI patients. We presented that dysfunctions of elbow, hip joint, and abnormal epiphyseal growth plate were associated with ectopic calcification and summarized the history of HPC progression and treatment. INTRODUCTION: The current study aims to systematically characterize the skeletal phenotypes of patients with type V OI and suggested possible surgical solutions. METHODS: A total of 28 patients were admitted for inpatient care at The Hong Kong University-Shenzhen Hospital diagnosed with type V OI (either clinically diagnosed or genetically confirmed with the IFITM5 c.-14C > T mutation). RESULTS: Prevalence of type V radiological features was comparable to previous literatures (RHD, 100%; CIM, 100%; HPC, 44%; and scoliosis, 50%). Novel skeletal phenotypes were presented including extension of coronoid process, acetabular labrum, acetabular protrusion, spontaneous autofusion of the hip, bulbous epiphysis, and popcorn calcification. Significant increase in BMD was observed in patients with bisphosphonate treatment. Twenty-five percent (3/12) of patients with preoperative use of indomethacin developed HPC postoperatively, and HPCs were absorbed in 2 young patients 2 years later. CONCLUSION: This retrospective study summarized the clinical features and highlighted the abnormalities in elbow, hip joint, and growth plate in type V OI patients. Our study contributed to a more comprehensive clinical spectrum of type V OI. We also characterized the natural progression of HPC formation and resorption in patients in different ages. The use of bisphosphonate treatment is effective in improving bone mineral density in type V OI patients, and whether indomethacin can reduce incidence of HPC formation deserves further investigation.
Subject(s)
Calcinosis , Osteogenesis Imperfecta , Humans , Osteogenesis Imperfecta/complications , Osteogenesis Imperfecta/drug therapy , Osteogenesis Imperfecta/genetics , Retrospective Studies , East Asian People , Mutation , Diphosphonates/therapeutic useABSTRACT
Accurate prediction of protein-ligand binding affinity is pivotal for drug design and discovery. Here, we proposed a novel deep fusion graph neural networks framework named FGNN to learn the protein-ligand interactions from the 3D structures of protein-ligand complexes. Unlike 1D sequences for proteins or 2D graphs for ligands, the 3D graph of protein-ligand complex enables the more accurate representations of the protein-ligand interactions. Benchmark studies have shown that our fusion models FGNN can achieve more accurate prediction of binding affinity than any individual algorithm. The advantages of fusion strategies have been demonstrated in terms of expressive power of data, learning efficiency and model interpretability. Our fusion models show satisfactory performances on diverse data sets, demonstrating their generalization ability. Given the good performances in both binding affinity prediction and virtual screening, our fusion models are expected to be practically applied for drug screening and design. Our work highlights the potential of the fusion graph neural network algorithm in solving complex prediction problems in computational biology and chemistry. The fusion graph neural networks (FGNN) model is freely available in https://github.com/LinaDongXMU/FGNN.
Subject(s)
Algorithms , Neural Networks, Computer , Ligands , Computational Biology , Drug DesignABSTRACT
The association between HLA loci and haematological malignancy has been reported in certain populations. However, there are limited data for HLA loci at a high-resolution level with haematological malignancy in China. In this study, a total of 1115 patients with haematological malignancies (including 490 AML, 410 acute lymphoblastic leukaemia (ALL), 122 myelodysplastic syndrome [MDS] and 93 non-Hodgkin's lymphoma [NHL]) and 1836 healthy individuals as a control group in the Han population of Zhejiang Province, China, were genotyped for HLA-A, HLA-C, HLA-B, HLA-DRB1 and HLA-DQB1 loci at high resolution. The possible association between HLA alleles and haplotypes and haematologic malignancy was analysed. The allele frequencies (AFs) of HLA-A*02:05, HLA-A*02:06, HLA-A*32:01, HLA-B*35:03, HLA-B*54:01, HLA-B*55:07, HLA-DRB1*04:05, HLA-DRB1*15:01, HLA-DQB1*04:01 and HLA-DQB1*06:02 in the MDS patients were much higher than those in the control group (P < 0.05), while the AFs of HLA-C*07:02, HLA-DRB1*03:01, HLA-DRB1*14:54, HLA-DQB1*02:01 and HLA-DQB1*05:03 were obviously lower than those in the control group (p < .05). Interestingly, the differences in these HLA alleles in patients with MDS were not significant after applying Bonferroni correction (Pc > .05), except for HLA-A*02:06 (Pc < .01). There were 13, 6 and 10 HLA alleles with uncorrected significant differences (p < .05) among patients with AML, ALL and NHL, respectively, compared with those in the control group, but the differences in these HLA alleles were not significant after correction (Pc > .05). Compared to those of the control group, there were some haplotypes over 1.00% frequency in patients with AML, MDS and NHL patients with uncorrected significant differences (p < .05). However, none of them showed a significant difference after correction as well (Pc > .05). The study reveals that HLA-A*02:06 may lead to susceptibility to MDS, but none of the HLA alleles were associated with AML, ALL or NHL after correction. These data will help to further understand the role of HLA loci in the pathogenesis of haematological malignancy in China.
Subject(s)
Hematologic Neoplasms , Leukemia, Myeloid, Acute , Myelodysplastic Syndromes , Humans , HLA-C Antigens/genetics , HLA-DRB1 Chains/genetics , Alleles , Gene Frequency , HLA-B Antigens/genetics , Haplotypes , HLA-DQ beta-Chains/genetics , Myelodysplastic Syndromes/genetics , HLA-A Antigens/genetics , China/epidemiologyABSTRACT
Diseases and environmental stresses are two distinct challenges for virtually all living organisms. In light of evolution, cellular responses to diseases and stresses might share similar molecular mechanisms, but the detailed regulation pathway is not reported yet.We obtained the transcriptomes and translatomes from several NSCLC (non-small-cell lung cancer) patients as well as from different species under normal or stress conditions. We found that the translation level of gene ATF4 is remarkably enhanced in NSCLC due to the reduced number of ribosomes binding to its upstream open reading frames (uORFs). We also showed the evolutionary conservation of this uORF-ATF4 regulation in the stress response of other species. Molecular experiments showed that knockdown of ATF4 reduced the cell growth rate while overexpression of ATF4 enhanced cell growth, especially for the ATF4 allele with mutated uORFs. Population genetics analyses in multiple species verified that the mutations that abolish uATGs (start codon of uORFs) are highly deleterious, suggesting the functional importance of uORFs.Our study proposes an evolutionarily conserved pattern that enhances the ATF4 translation by uORFs upon stress or disease. We generalized the concept of cellular response to diseases and stresses. These two biological processes may share similar molecular mechanisms.
Subject(s)
Activating Transcription Factor 4/genetics , Carcinoma, Non-Small-Cell Lung , Lung Neoplasms , Open Reading Frames , Biological Phenomena , Carcinoma, Non-Small-Cell Lung/genetics , Codon, Initiator , Humans , Lung Neoplasms/genetics , Protein BiosynthesisABSTRACT
Fe3O4 magnetic nanoparticles (MNPs) have attracted tremendous attention due to their superparamagnetic properties, large specific surface area, high biocompatibility, non-toxicity, large-scale production, and recyclability. More importantly, numerous hydroxyl groups (-OH) on the surface of Fe3O4 MNPs can provide coupling sites for various modifiers, forming versatile nanocomposites for applications in the energy, biomedicine, and environmental fields. With the development of science and technology, the potential of nanotechnology in the food industry has also gradually become prominent. However, the application of composite Fe3O4 MNPs in the food industry has not been systematically summarized. Herein, this article reviews composite Fe3O4 MNPs, including their properties, modifications, and physical functions, as well as their applications in the entire food industry from production to processing, storage, and detection. This review lays a solid foundation for promoting food innovation and improving food quality and safety.
ABSTRACT
Water molecules at the ligand-protein interfaces play crucial roles in the binding of the ligands, but the behavior of protein-bound water is largely ignored in many currently used machine learning (ML)-based scoring functions (SFs). In an attempt to improve the prediction performance of existing ML-based SFs, we estimated the water distribution with a HydraMap (HM) method and then incorporated the features extracted from protein-bound waters obtained in this way into three ML-based SFs: RF-Score, ECIF, and PLEC. It was found that a combination of HM-based features can consistently improve the performance of all three SFs, including their scoring, ranking, and docking power. HydraMap-based features show consistently good performance with both crystal structures and docked structures, demonstrating their robustness for SFs. Overall, HM-based features, which are a statistical representation of hydration sites at protein-ligand interfaces, are expected to improve the prediction performance for diverse SFs.
Subject(s)
Machine Learning , Water , Ligands , Molecular Docking Simulation , Protein Binding , Proteins/chemistryABSTRACT
BACKGROUND: Thyroid disease is one of the common endocrine disorders affecting the pregnant women, in which thyroid autoimmunity can alter the progress and the outcome of pregnancy. Women with euthyroid status but anti-thyroid peroxidase (anti-TPO) antibodies positivity before pregnancy are prone to subclinical gestational hypothyroidism. However, the connections between anti-TPO antibodies positivity and gestational hypothyroidism remain largely unknown. The aim of the present study is to investigate the differences of fetal metabolic profile at birth according to maternal anti-TPO status. METHODS: We performed 1H-NMR metabolomics on cord blood of a nested case control cohort of 22 pregnant women with matched thyroid hormone levels and demographic data, including 11 women with euthyroid status but anti-thyroid antibodies positivity (into the anti-TPO antibodies positivity group) and 11 matched women as controls with euthyroid status and negative anti-thyroid antibodies (into the control group). RESULTS: Distinct metabolic profiles were observed between the anti-TPO antibody positivity group and the nested control group, from which a total of 10 metabolites with between-group altered abundances were structurally identified. Five out of the 10 metabolites were up-regulated in the anti-TPO antibodies positivity group, including D-Glucose, L-Glutamine, 3-Hydroxybutyric acid, Myo-Inositol, Creatinine. The other 5 metabolites were down-regulated in the anti-TPO antibodies positivity group, including L-Leucine, L-Lysine, L-Glutamic acid, L-Tyrosine, and L-Phenylalanine. All the 10 metabolites have been previously reported to be correlated with hypothyroidism. Metabolite set enrichment analysis and pathway analysis suggested that amino acid metabolism pathways (especially the phenylalanine metabolism) were associated with anti-TPO antibodies positivity. CONCLUSION: The results of this study suggested that fetal metabolic disorder is correlated with anti-TPO antibodies positivity, representing by abundance alteration of hypothyroidism associated metabolites and the related disturbance of amino acid metabolism pathways.
Subject(s)
Hypothyroidism , Metabolic Diseases , Autoantibodies , Female , Fetal Blood , Humans , Infant, Newborn , Metabolomics , PregnancyABSTRACT
OBJECTIVE: To detect loss of heterozygosity (LOH) at human leukocyte antigen (HLA) loci in a Chinese patient with leukemia after haploidentical hematopoietic stem cell transplantation. METHODS: HLA genotyping was carried out on peripheral blood, hair follicle and buccal swab samples derived from the patient after the transplantation as well as peripheral blood samples from his parents by using PCR-sequence specific oligonucleotide probe method and PCR-sequence based typing method. Short tandem repeat (STR) loci were detected by using a 23 site STR assay kit and a self-developed 6 STR loci assay for the HLA regions. RESULTS: After the transplantation, the HLA genotype of the peripheral blood sample of the patient was identical to his father. The patient was HLA-A*02:01,24:02, C*03:03,03:04, B*13:01,15:01, DRB1*08:03,12:02, DQB1*03:01,06:01 for his hair follicle specimen. However, homozygosity of the HLA loci was found in his buccal swab sample. Only the HLA-A*24:02-C*03:03-B*15:01-DRB1*08:03-DQB1*06:01 haplotype from his father's was present, while the HLA-A*02:01-C*03:04-B*13:01-DRB1*12:02-DQB1*03:01 haplotype from his mother was lost. After the transplantation, the alleles of the 23 STR sites in the patient's peripheral blood sample were consistent to his father, with no allelic loss detected in his buccal swab sample. However, at least 4 STR loci in the HLA region were lost in his buccal swab sample. CONCLUSION: LOH at the HLA loci has been detected in the buccal swab sample of a patient with leukemia who received haploidentical hematopoietic stem cell transplantation.
Subject(s)
HLA Antigens , Leukemia , HLA Antigens/genetics , HLA-A Antigens/genetics , Histocompatibility Antigens Class I/genetics , Humans , Leukemia/genetics , Loss of HeterozygosityABSTRACT
This work investigated the clinical prognostic implications and biological function of plasma soluble programmed cell death ligand 1 in breast cancer patients. Plasma sPD-L1 levels of recurrent/metastatic breast cancer patients were determined, and the association of sPD-L1 levels and metastatic progression-free survival and metastatic overall survival was assessed. The PD-L1 expression on breast cancer cells was analyzed by flow cytometry, and the level of sPD-L1 in the supernatant of breast cancer cells was determined by enzyme-linked immunosorbent assay. Furthermore, the effect of sPD-L1 on the proliferation and apoptosis of T lymphocytes was detected by WST-1 assay and flow cytometry. The plasma sPD-L1 levels in 208 patients with recurrent/metastatic breast cancer before receiving first-line rescue therapy were measured. The optimal cutoff value of plasma sPD-L1 for predicting disease progression was 8.774 ng/ml. Univariate and multivariate analyses identified high sPD-L1 level (≥ 8.774 ng/ml) and visceral metastasis were independent factors associated with poor prognosis. Relevance analysis showed that the plasma sPD-L1 level was weaklyassociated with some systemic inflammation markers, including white cell count (WBC), absolute monocytecount, and absolute neutrophil count. Furthermore, we found sPD-L1 could be found in supernatant of culture with breast cancer cell line expressing PD-L1 on the cell surface and inhibit T lymphocyte function, playing a negative regulatory role in cellular immunity. sPD-L1 was a good tumor predictive maker in breast cancer and it may play a potentially important role in immune tolerance.
Subject(s)
Breast Neoplasms/drug therapy , T-Lymphocytes/metabolism , Breast Neoplasms/mortality , Cell Line, Tumor , Female , Humans , Middle Aged , Progression-Free SurvivalABSTRACT
PREMISE: Leaf mass (M) and lamina surface area (A) are important functional traits reported to obey a scaling relationship called "diminishing returns" (i.e., M â Aα>1 ). Previous studies have focused primarily on eudicots and ignored whether the age of leaves affects the numerical value of the scaling exponent (i.e., α). METHODS: The effect of age was examined using 1623 Phyllostachys edulis leaves from culms differing in age collected in Nanjing, China. The scaling relationships among leaf A, fresh mass (FM), and dry mass (DM) were evaluated using reduced major axis protocols. The bootstrap percentile method was used to test the significance of differences in α-values. RESULTS: Overall, the numerical values of α exceeded 1.0. The scaling relationship between FM and A was statistically more robust than that between DM and A. The scaling exponents of FM vs. A exhibited a "high-low-high-low-high" numerical trend from the oldest to the youngest age-group. FM increased linearly as culm age decreased; the leaf DM per unit area (LMA) exhibited a parabolic trend across the age-groups. CONCLUSIONS: "Diminishing returns" is confirmed for all but one age-group of an important monocot species. The relationship between FM and A was statistically more robust than that between DM and A for each age-group. The FM per unit A decreased with increasing age-groups, whereas the middle age-groups had a greater LMA than the oldest and youngest age-groups. These data are the first to show that the age of shoots affects the scaling relationship between leaf mass and area.
Subject(s)
Plant Leaves , Poaceae , ChinaABSTRACT
The distributions of HLA allele and haplotype are various in the populations. Currently, the data for HLA alleles and haplotypes at three fields resolution level in Chinese Han population is rare. Here, the HLA alleles and haplotypes of the 1734 cord blood samples from Zhejiang Han population, China were reported at three fields resolution. All samples were randomly collected from the Zhejiang Cord Blood Bank, China. HLA-A, -B, -C, -DRB1, -DQB1, -DRB3/4/5 loci was genotyped using next generation sequencing method. The genotypes of the samples were assigned using the HLA TypeStream Visual Software version 1.2.0. The frequency of alleles, haplotype estimation and linkage disequilibrium analysis were performed with the Arlequin software 3.5.2.2. It was found that the top three frequent alleles of HLA-A, -B, -C, -DRB1, -DQB1, -DRB3/4/5 loci were A*11:01:01 (25.81%), A*24:02:01 (16.70%), A*02:01:01 (10.61%); B*40:01:02 (15.97%), B*46:01:01 (11.48%), B*58:01:01 (7.96%); C*07:02:01 (19.03%), C*01:02:01 (17.65%), C*03:04:01 (10.41%); DRB1*09:01:02G (17.96%), DRB1*12:02:01 (9.57%), DRB1*08:03:02 (9.54%); DQB1*03:01:01G (21.05%), DQB1*03:03:02 (19.15%), DQB1*06:01:01G (12.08%); DRB4*01:03:01 (25.72%), DRB3*02:02:01 (20.27%), DRB5*01:01:01 (10.96%), respectively. A total of 1528 distinct Aâ¼Câ¼Bâ¼DRB3/4/5â¼DRB1â¼DQB1 haplotypes were estimated, and the top three most common haplotypes were A*33:03:01â¼C*03:02:02â¼B*58:01:01â¼DRB3*02:02:01â¼DRB1*03:01:01â¼ DQB1*02:01:01 (4.02%), A*30:01:01â¼C*06:02:01â¼B*13:02:01â¼DRB4*01:03:01â¼ DRB1*07:01:01 â¼DQB1*02:02:01 (3.11%) and A*02:07:01â¼C*01:02:01â¼B*46:01:01 â¼DRB4*01:03:01â¼DRB1*09:01:02Gâ¼DQB1*03:03:02 (3.05%). Some alleles of different HLA loci were shown strong linkage disequilibrium. In conclusion, the data of allele and haplotype of HLA-A, -B, -C, -DRB1, -DQB1 and -DRB3/4/5 loci at three fields resolution level were obtained in Zhejiang Han population, thus contributing to analyze the HLA ploymorphism in the populations.
Subject(s)
HLA-A Antigens , Technology , Alleles , China , Gene Frequency , HLA-A Antigens/genetics , HLA-DRB1 Chains/genetics , Haplotypes , HumansABSTRACT
The NF1 gene encodes neurofibromin, which is one of the primary negative regulatory factors of the Ras protein. Neurofibromin stimulates the GTPase activity of Ras to convert it from an active GTP-bound form to its inactive GDP-bound form through its GTPase activating protein-related domain (GRD). Therefore, neurofibromin serves as a shutdown signal for all vertebrate RAS GTPases. NF1 mutations cause a resultant decrease in neurofibromin expression, which has been detected in many human malignancies, including NSCLC, breast cancer and so on. NF1 mutations are associated with the underlying mechanisms of treatment resistance discovered in multiple malignancies. This paper reviews the possible mechanisms of NF1 mutation-induced therapeutic resistance to chemotherapy, endocrine therapy and targeted therapy in malignancies. Then, we further discuss advancements in targeted therapy for NF1-mutated malignant tumors. In addition, therapies targeting the downstream molecules of NF1 might be potential novel strategies for the treatment of advanced malignancies.
ABSTRACT
Transition-metal dichalcogenides (TMDCs) have attracted a lot of attention due to their electronic, optical, mechanical, and catalytic properties. In addition, TMDCs possess rich redox chemistry that enables the decoration of metal nanoparticles directly on their surfaces. In this paper, MnO2/MoS2 nanocomplexes were obtained by the spontaneous reduction of KMnO4 with MoS2 QDs as the reductive agent. The formed MnO2/MoS2 nanocomplexes exhibited activated fluorescence and MR imaging signal in the presence of glutathione (GSH). After conjugation with an AS1411 aptamer, specific in vivo MR imaging and fluorescence labeling of the 786-O tumor cells were realized, showing their promising potential for biomedical applications.
Subject(s)
Disulfides/chemistry , Glutathione/chemistry , Molybdenum/chemistry , Potassium Permanganate/chemistry , Quantum Dots/chemistry , Animals , Aptamers, Nucleotide/chemistry , Biocompatible Materials/chemistry , Biocompatible Materials/pharmacology , Cell Line, Tumor , Cell Survival/drug effects , Humans , Magnetic Resonance Imaging , Mice , Mice, Inbred BALB C , Neoplasms/diagnostic imaging , Neoplasms/pathology , Oxidation-Reduction , Quantum Dots/toxicityABSTRACT
Liver-regulating herb compound (LRHC) has good effects on improving sperm quality and male fertility of varicocele (VC) patients. But the mechanism of LRHC on VC is still not clear. This study explored the effects of LRHC on histomorphological and ultrastructural changes and expression of stem cell factor (SCF) and C-KIT of VC rat testis. Twenty-four male rats were divided into three groups with eight rats in each group as sham, varicocele and LRHC groups. Testis specimens were collected for light microscopy and transmission electron microscopy respectively. The expression of SCF/C-KIT was detected with Western blot. Results showed that seminiferous tubules in VC rats were damaged and cell numbers were decreased. Ultrastructural alterations were observed, such as increased thickness of lamina propria, vacuolation in Sertoli cells, spermatocytes and spermatids, and abnormal head and mitochondria in spermatozoa. While in LRHC-treated rats, the architectures of seminiferous tubules were as organised and compact as that of sham animals, and ultrastructure of Sertoli, Leydig and germ cells developed well. LRHC ameliorated histological appearance and ultrastructure by VC. In addition, the abnormal expression of SCF and C-KIT were observed in testicular tissues from rats with VC, which were brought back to normal level by LRHC.
Subject(s)
Varicocele , Animals , Humans , Liver , Male , Rats , Seminiferous Tubules , Spermatids , TestisABSTRACT
PURPOSE: This study aimed to investigate the clinical outcomes of morula stage transfer derived from post-thawed cleavage embryos undergoing overnight culture in frozen embryo transfer (FET) cycles. METHODS: We performed a retrospective study that included 392 FET cycles with 784 thawed embryos undergoing overnight culture between January 2014 and December 2018. Embryos were divided into three groups in terms of their status: 8-16 cells without morula (group I), one morula (group II), and two morulae (group III). The clinical outcomes of these cycles were then compared between the three groups. Logistic regression analysis was performed to control for confounders. RESULTS: Group III was associated with a significantly higher clinical pregnancy rate (odds ratio [OR] 2.35; 95% confidence interval [CI] 1.29-4.27; P = 0.005), implantation rate (OR 3.00; CI 1.75-5.16; P < 0.001), multiple pregnancy rate (OR 4.91; CI 2.11-11.40; P < 0.001), and live birth rate (OR 1.96; CI 1.10-3.49; P = 0.022) than group I. Group II had a higher live birth rate than group I after adjustment (OR 1.70; CI 1.04-2.79; P = 0.035). There was no difference in the rate of premature delivery when compared across the three groups after adjustment. CONCLUSION: The transfer of morula stage embryos following the overnight culture of post-thawed cleavage embryos led to an improvement in the clinical outcomes of FET cycles. It is important to reduce the number of morula embryos transferred in order to achieve a singleton pregnancy.
Subject(s)
Cleavage Stage, Ovum/transplantation , Embryo Transfer , Fertilization in Vitro , Morula/transplantation , Adult , Birth Rate , Cryopreservation , Embryo Implantation/genetics , Female , Humans , Morula/cytology , Ovulation Induction , Pregnancy , Pregnancy Rate , Retrospective StudiesABSTRACT
"Bottom-up" method is a popular approach for the preparation of molybdenum disulfide quantum dots (MoS2 QDs) benefitting from less time consumption and no high-powered sonication required. But the relatively low fluorescent quantum yield of the obtained MoS2 QDs and the rare study about their in vivo behavior stimulate us to do more research in this area. In this paper, we proposed a "bottom-up" hydrothermal method to prepare MoS2 QDs with a quantum yield (QY) of 34.55% by optimizing a series of reaction conditions. The successful fluorescence imaging of tumor cells in vitro and in vivo as well as the systematic in vivo behavior study such as biocompatibility, biodistribution and metabolism route provided the good basis for their wider biomedical applications.