A loss-of-function variant in ZCWPW1 causes human male infertility with sperm head defect and high DNA fragmentation.

BACKGROUND: Male infertility is a global health issue. The more causative genes related to human male infertility should be further explored. The essential role of Zcwpw1 in male mouse fertility has been established and the role of ZCWPW1 in human reproduction needs further investigation to verify. METHODS: An infertile man with oligoasthenoteratozoospermia phenotype and his parents were recruited from West China Second University Hospital, Sichuan University. A total of 200 healthy Han Chinese volunteers without any evidence of infertility were recruited as normal controls, while an additional 150 infertile individuals were included to assess the prevalence of ZCWPW1 variants in a sporadic male sterile population. The causative gene variant was identified by Whole-exome sequencing and Sanger sequencing. The phenotype of the oligoasthenoteratozoospermia was determined by Papanicolaou staining, immunofluorescence staining and electron microscope. In-vitro experiments, western blot and in-silicon analysis were applied to assess the pathogenicity of the identified variant. Additionally, we examined the influence of the variant on the DNA fragmentation and DNA repair capability by Sperm Chromatin Dispersion and Neutral Comet Assay. RESULTS: The proband exhibits a phenotype of oligoasthenoteratozoospermia, his spermatozoa show head defects by semen examination, Papanicolaou staining and electron microscope assays. Whole-exome sequencing and Sanger sequencing found the proband carries a homozygous ZCWPW1 variant (c.1064C > T, p. P355L). Immunofluorescence analysis shows a significant decrease in ZCWPW1 expression in the proband's sperm. By exogenous expression with ZCWPW1 mutant plasmid in vitro, the obvious declined expression of ZCWPW1 with the mutation is validated in HEK293T. After being treated by hydroxyurea, MUT-ZCWPW1 transfected cells and empty vector transfected cells have a higher level of γ-H2AX, increased tail DNA and reduced H3K9ac level than WT-ZCWPW1 transfected cells. Furthermore, the Sperm Chromatin Dispersion assay revealed the proband's spermatozoa have high DNA fragmentation. CONCLUSIONS: It is the first report that a novel homozygous missense mutation in ZCWPW1 caused human male infertility with sperm head defects and high DNA fragmentation. This finding enriches the gene variant spectrum and etiology of oligoasthenoteratozoospermia.

Maintenance of cell integrity during hydroxyl radical rapid inactivation of Pseudanabaena sp. and simultaneous mineralization of odor compound 2-methylisoborneol.

Pseudanabaena sp. and the odor compound it produces, 2-methylisoborneol (2-MIB), has been reportedly responsible for off-flavor pollution worldwide, leading to substandard drinking water sensory indicators and serious water supply crises. In this paper, the hydroxyl radical (•OH) produced by the synergistic effect of strong ionization discharge and hydrodynamic cavitation rapidly inactivated Pseudanabaena sp. and simultaneously mineralized 2-MIB to a concentration of 2.57 ng/L, which is below the odor threshold of 10 ng/L for a total reactive oxidants (TRO) concentration of 1.2 mg/L within 12 s. Crucially, the intracellular 2-MIB level was maintained in approximately 155.26- 162.29 ng/L range, indicating that 2-MIB was not released from the cells. Based on the scanning electron microscopy (SEM) results, the integrity of Pseudanabaena sp. cells was maintained with intact membranes and no intracellular organic matters (IOM) released during •OH inactivation. In contrast, ClO2 caused severe membrane rupture and massive IOM release. Based on the gas chromatograph/mass spectrometer (GC/MS) analyses and mass spectral database, the chromatogram fitted the baseline with a TRO concentration of 4 mg/L and no peaks corresponding to intermediates were detected. Moreover, •OH could mineralize 2-MIB by opening the ring structures of 1,2,3,3-tetramethyl-4-cyclopentenone, neomenthol, and 2-methylcyclohexene-1-aldehyde to produce small-molecule compounds, finally leading to CO2 and H2O formation via three reaction pathways. Therefore, the •OH not only maintained the cell integrity of Pseudanabaena sp. during inactivation but also mineralized 2-MIB simultaneously.

Dust deposition mechanism and output characteristics of solar bifacial PV panels.

The utilization of solar photovoltaic (PV) power generation represents a highly promising technological solution for addressing environmental challenges and energy crises. Dust deposition on the front and back surfaces of solar bifacial PV panels greatly decreases the optical performance and power generation. In this study, the dust deposition characteristics and mechanism of solar bifacial PV panels are investigated using the CFD-DEM method. The effects of the dust deposition rate on the output characteristics of bifacial PV panels are discussed. The research results show that the particle deposition behaviors on the back and front surfaces of bifacial PV panels are influenced by the deposition and separation forces at the left or right inlets. The dust deposition rate of windward surfaces can be 1.48-7.60 times that of the leeward surfaces of bifacial PV panels. The particle motion trajectories on the windward and leeward sides can be mainly divided into five and three kinds, respectively. The dust deposition rate of bifacial PV panels increases when the air inlet velocity decreases and the particle size and concentration and relative humidity increase. The open circuit voltage and short circuit current of bifacial PV panels decreased by 26.7% and 16.4%, respectively, when the dust deposition rate increases by 45.8%. The attenuation rate of the maximum output power of PV panels has a positive linear correlation with the dust deposition rate, as shown in Eq. 22. The bifacial PV panels have better output characteristics than the mono-facial PV panels with consideration of dust deposition.

Multiple metastases of clear cell sarcoma at diagnosis presented in bone marrow aspirate: A case report.

Clear cell sarcoma (CCS) is a rare and aggressive soft-tissue sarcoma that arises most commonly in adolescents and young adults of both sexes. CCS presents a diagnostic challenge due to its morphological and immunohistochemical similarity to malignant melanoma. We present a rare and severe case of CCS simultaneously with multiple bone and lymph node metastases at the time of initial diagnosis in a previously healthy 15-year-old Chinese man. Detailed information on clinical manifestations, laboratory profiles, histopathological findings and poor outcome were described. The cytomorphology of bone marrow aspirate in CCS in Wright-Giemsa staining smear was first depicted in this case. The diagnostic difficulties of the rare case was also discussed.

Ready-to-implement low-carbon retrofit of coal-fired power plants in China: Optimal scenarios selection based on sludge and photovoltaic utilization.

Currently the flexible demand for high proportion penetration of renewable energy depends on coal-fired units (CFUs), and the large-scale phase-out of CFUs in a short time is not realistic in China. Due to urban expansion, approximately 458 Chinese coal-fired power plants (CFPPs) are now located in cities. Limited by space, urban CFUs face difficulty in becoming equipped with carbon capture and storage systems. This presents a sizeable challenge for the low-carbon transition of urban CFPPs and carbon neutral processes. Here, we present a ready-to-implement method to reduce the carbon emission of CFPPs in limited space: roof photovoltaic-assisted power generation combined with sludge co-combustion for coal-fired power generation systems (PVSCs). We also consider nonurban CFPPs with the method of roof photovoltaic-assisted power generation (PVs) only. Based on remaining life cycle analysis, we find that the PVSCs could save 28.47 Mt of coal, reduce CO2 emissions by 69.76 Mt, treat 125.70 Mt of sludge, and also generate 12.08 billion RMB worth of electricity revenue per year. In addition, our scenario analysis shows that PVSCs are more profitable when choosing an urban CFU with a remaining life of more than 12 years and while the sludge treatment subsidy is set at 100 RMB t-1. Under strict and lenient CFU decommissioning policies, CFUs with a remaining life of between 19 and 30 years and between 13 and 24 years should be selected for PVs, respectively. Thus, we conclude that PVSCs can not only generate economic benefits but also facilitate carbon reduction and solid waste treatment.

A Deep Learning Model for the Automatic Recognition of Aplastic Anemia, Myelodysplastic Syndromes, and Acute Myeloid Leukemia Based on Bone Marrow Smear.

Aim: Bone marrow biopsy is essential and necessary for the diagnosis of patients with aplastic anemia (AA), myelodysplastic syndromes (MDS), and acute myeloid leukemia (AML). However, the convolutional neural networks (CNN) model that automatically distinguished AA, MDS, and AML based on bone marrow smears has not been reported. Methods: Image-net pretrained model of CNN was used to construct the recognition model. Data extracted from the American Society of Hematology (ASH) Image Bank were utilized to develop the model and data extracted from the clinic were used for external validation. The model had two output layers: whether the patient was MDS (two-classification) and which of AA, MDS, and AML the patient was (three-classification). Different outcome weights (two-classification/three-classification = 5:5, 2:8, 1:9) and epochs (30, 50, 200) were used to select the optimal model. The model performance was evaluated by the Accuracy-Loss curves and calculating the area under the curve (AUC), accuracy, sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV). Results: A total of 115 bone marrow smears from the ASH Image Bank and 432 bone marrow smears from the clinic were included in this study. The results of Accuracy-Loss curves showed that the best model training effect was observed in the model with the outcome weight and epoch of 1:9 and 200. Similarly, this model also performed well performances in the two-classification of MDS and the three-classification of AA, MDS, AML. The AUC, accuracy and sensitivity of the MDS two-classification model in the testing set were 0.985 [95% confidence interval (CI), 0.979-0.991], 0.914 (95%CI, 0.895-0.934), and 0.992 (95%CI, 0.980-1.000), respectively. The AUC, accuracy and sensitivity of the AA, MDS, AML three-classification model in the testing set were 0.968 (95%CI, 0.960-0.976), 0.929 (95%CI, 0.916-0.941), and 0.857 (95%CI, 0.828-0.886), respectively. Conclusion: The image-net pretrained model was able to obtain high accuracy AA, MDS, AML distinction, and may provide clinicians with a convenient tool to distinguish AA, MDS, and AML.

Liquid bridges between particles and the hydrophobic or hydrophilic surfaces of solar photovoltaic glass.

Photovoltaic (PV) power generation technology is one of the most important methods for reaching the carbon peak and achieving carbon neutralization. Dust accumulation on the surface of PV glass greatly reduces the working performance and power generation efficiency of PVs. The hydrophobic or hydrophilic surfaces on the PV glass have substantial self-cleaning potential. In this study, the liquid bridges formed between particles and the hydrophobic or hydrophilic surfaces of solar PV glass are investigated. The effects of the liquid bridge force and the influencing factors for these two surfaces on particle dynamics behaviours are studied. Furthermore, the self-cleaning abilities of these two surfaces are also discussed. The results indicate that the liquid bridges formed between a particle and a hydrophilic PV glass placed horizontally or obliquely exhibit similar saddle shapes, but the liquid bridges wrap the particle on the surface of hydrophobic PV glass. The influence of the liquid bridges causes particles to adhere to the tilted hydrophilic or hydrophobic surfaces at liquid bridge volumes (VL) < 6 µL, making initially moving particles stay on these two tilted surfaces with 6 µL ≤ VL ≤ 20 µL and even achieving self-cleaning properties at VL > 20 µL. Both hydrophobic and hydrophilic surfaces increase the self-cleaning forces resulting from the liquid bridge formation with increasing VL, thus completing the self-cleaning process. Increasing the self-cleaning forces and decreasing the friction force and the liquid bridge force improves the self-cleaning abilities of the surface. These research findings have important theoretical significance and commercial engineering value in preventing and reducing dust accumulation on glass.

Influence mechanism of liquid bridge evaporation on the dynamic behaviour of dust particles on solar photovoltaic panels.

Solar photovoltaics (PVs) are one of the most promising renewable energy sources to solve the global environmental and energy crises. Dust agglomeration on PV panels greatly affects their operation life and power generation efficiency. In this study, the evaporation mechanism and laws of liquid bridges as well as the evaporation time and interaction forces for liquid bridges and particles are investigated. The effects of liquid bridge evaporation and its influencing factors on dust dynamic behaviour are discussed. Liquid bridge evaporation in the muddy state with small particle spacing can cause particle agglomeration on PV panels. However, it is very difficult for the capillary, the ribbon, and the pendulum states or the muddy state with large particle spacing to affect particle motion. In the muddy state, the interaction force for a small particle spacing consists of not only the liquid bridge force but also the drag force caused by liquid bridge evaporation, and that for a large particle spacing consists of only the drag force; in the other three states, the interaction force consists of only the liquid bridge force. Liquid bridge evaporation can greatly intensify particle agglomeration and even scaling processes with decreasing particle size. These findings can provide important theoretical guidance and value for engineering improvements in power generation and safe operation of PV panels.

Exosome long non-coding RNA SOX2-OT contributes to ovarian cancer malignant progression by miR-181b-5p/SCD1 signaling.

Ovarian cancer is a common gynecologic cancer with increased mortality and morbidity. Exosome-delivered long non-coding RNAs have been well found in cancer development. However, the function of exosomal SOX2-OT in ovarian cancer development is still unreported. In the present study, we were interested in the investigation of the effect of exosomal SOX2-OT during ovarian cancer pathogenesis. Significantly, we revealed that the SOX2-OT expression levels were up-regulated in the ovarian cancer patients' plasma exosomes. The depletion of exosomal SOX2-OT inhibited migration, invasion, and proliferation and induced apoptosis in ovarian cancer cells. In mechanical exploration, SOX2-OT could sponge miR-181b-5p, and miR-181b-5p was able to target SCD1 in the ovarian cancer cells. The SCD1 overexpression and miR-181b-5p inhibitor could reverse exosomal SOX2-OT-mediated ovarian cancer progression. Functionally, the depletion of exosomal SOX2-OT significantly reduced tumor growth of ovarian cancer cells in vivo. In summary, we concluded that exosomal SOX2-OT enhanced ovarian cancer malignant phenotypes by miR-181b-5p/SCD1 axis. Our finding presents novel insights into the mechanism by which exosomal lncRNA SOX2-OT promotes ovarian cancer progression. SOX2-OT, miR-181b-5p, and SCD1 may serve as potential targets for the treatment of ovarian cancer.

Study of a dust deposition mechanism dominated by electrostatic force on a solar photovoltaic module.

Solar energy is one of the most promising renewable energy sources to solve the energy crisis. Dust deposition on solar photovoltaic (PV) modules significantly reduces the power generation of PV power plants. In this paper, the motion characteristics of the gas phase and charging mechanism of dust particles and solar PV glass are investigated by means of the computational fluid dynamics-discrete element model (CFD-DEM) method. In addition, the mechanism and characteristics of dust deposition on a solar PV module as dominated by electrostatic force are discussed. The research results show that frequent collisions between dust particles and PV glass or between dust particles lead to charging. The dust deposition mechanism on a solar PV module is a gas-solid-electrical multi-directional coupling process. There is a great electrostatic field near the solar PV glass, causing charged dust particle deposition. The dust deposition density decreases when the air inlet velocity increases and when the tilt angle of the solar PV module or the number of particle collisions decreases. Different particle dynamics have different dust deposition ratios for different predominant deposition forces (such as the electrostatic force, van der Waals force, and gravity force). The research findings provide an important theoretical basis for dust deposition prevention and removal from solar PV modules.

T-cell blast crisis of chronic myelogenous leukemia presented with coexisting p210 and p190 BCR-ABL transcripts and t(10;11)(q11;p15).

BACKGROUND: Blast transformation of chronic myelogenous leukemia (CML) to T lymphoblastic lymphoma/acute lymphoblastic leukemia (T-LBL/ALL) is rare, and the molecular mechanism is still unclear. CASE REPORT: A 28-year-old woman who developed T-ALL with coexpressing both p210 and p190 BCR-ABL transcripts five years after the initial diagnosis of CML in chronic phase. The proliferation of bone marrow was extremely active with blast cells over 20%. Chromosome analysis revealed t(9;22)(q34;q11) and t(10;11)(q25;p15). Flow immunophenotyping showed that blasts expressed CD4, CD7, CD11b, CD38, CD34, CD33, and cCD3. CONCLUSION: It is the first T-cell blast of CML case with coexisting p210 and p190 as well as additional chromosome translocations. Through review this case and previous reports, we will reveal that CML patients with T-lymphocyte transformation depend on potential molecular and pathological mechanism.

Ongoing change of severe hand, foot, and mouth disease pathogens in Yunnan, China, 2012 to 2016.

Hand, foot, and mouth disease (HFMD) is a common infectious disease caused by enteroviruses (EVs). In this study, a total of 341 children with serious HFMD were admitted to a pediatric hospital in Yunnan, China in 2012 to 2016. EVs were detected in 283 specimens (83.0%) and were assigned to 17 EV types. Enterovirus A71 (EV-A71) was predominant, accounting for 41.6%, and was followed by coxsackievirus A16 (CV-A16; 18.8%), CV-A6 (9.1%), CV-A10 and E-9 (2.9%), CV-B5 (1.8%), CV-A9 (1.2%), E-30 (0.9%), E-18, CV-A4, C-B3, and CV-A2 (0.6%) and other EV types such as CV-A8, CV-A14, E-14, E-11, and CV-B4 (0.3%). All of the EV-A71 isolates belonged to C4a; the CV-A16 belonged to B1b or B1a, although the B1b strains were predominant; and CV-A6 belonged to D3. In 2012 to 2014, E-9 was the third most frequent serotype (8.2%, 5.0%, and 6.5%, respectively). E-9 was not detected in 2015 and 2016. CV-A6 was not detected in 2012 but was the second most frequent serotype (25.3%) in 2015. Active etiological surveillance of HFMD makes it necessary to be aware of these emerging pathogens.

Acute pro-B-Cell lymphoblastic leukemia transformed from myelodysplastic syndrome with an ASXL1 missense mutation: A case report with literature review.

The development of acute lymphoblastic leukemia (ALL) from myelodysplastic syndrome (MDS) is a very rare event. The current report presents a rare case of a 33-year-old man who was diagnosed with MDS with multiple-lineage dysplasia (MDS-MLD) that transformed into pro-B-ALL. A missense mutation (S1231F) of the additional sex combs like 1, transcriptional regulator gene was identified, which may have a substantial role in the progression, however does not act as an unfavorable prognostic marker. The patient died during induction chemotherapy. The present study further conducted an analysis on 30 patients to determine progression to ALL. Patients were predominantly male (76.7%, 23/30) with a median age of 56 years (3-90 years). The median time to transformation was 5.5 months (2-50 months). The most common type of MDS with ALL transformation comprised of MDS-excess blasts (MDS-EB; 40%, 12/30), MDS with single-lineage dysplasia (MDS-SLD; 30%, 9/30) and MDS with ring sideroblasts (MDS-RS; 16.7%, 5/30). The majority of the patients transformed to B-cell (66.7%, 16/24) followed by T-cell (33.3%, 8/24) ALL. From the 25 cases where data was available, the complete remission rate was 75% (15/20) with ALL-directed chemotherapy and the median remission duration was 15 months (range 4.5 to 51 months). However, the results indicated that ALL following MDS is characterized by a high rate of early death (20%, 5/25).

Frequencies, Laboratory Features, and Granulocyte Activation in Chinese Patients with CALR-Mutated Myeloproliferative Neoplasms.

Somatic mutations in the CALR gene have been recently identified as acquired alterations in myeloproliferative neoplasms (MPNs). In this study, we evaluated mutation frequencies, laboratory features, and granulocyte activation in Chinese patients with MPNs. A combination of qualitative allele-specific polymerase chain reaction and Sanger sequencing was used to detect three driver mutations (i.e., CALR, JAK2V617F, and MPL). CALR mutations were identified in 8.4% of cases with essential thrombocythemia (ET) and 5.3% of cases with primary myelofibrosis (PMF). Moreover, 25% of polycythemia vera, 29.5% of ET, and 48.1% of PMF were negative for all three mutations (JAK2V617F, MPL, and CALR). Compared with those patients with JAK2V617F mutation, CALR-mutated ET patients displayed unique hematological phenotypes, including higher platelet counts, and lower leukocyte counts and hemoglobin levels. Significant differences were not found between Chinese PMF patients with mutants CALR and JAK2V617F in terms of laboratory features. Interestingly, patients with CALR mutations showed markedly decreased levels of leukocyte alkaline phosphatase (LAP) expression, whereas those with JAK2V617F mutation presented with elevated levels. Overall, a lower mutant rate of CALR gene and a higher triple-negative rate were identified in the cohort of Chinese patients with MPNs. This result indicates that an undiscovered mutant gene may have a significant role in these patients. Moreover, these pathological features further imply that the disease biology varies considerably between mutants CALR and JAK2V617F.

A tetraploid minimally differentiated acute myeloblastic leukemia with extensive erythrophagocytosis: a case report and literature review.

Tetraploidy is a rare chromosome number aberration in de novo acute myeloid leukemia (AML), and may be associated with erythrophagocytosis by leukemic blast cells. We report a 48-year-old female patient with minimally differentiated acute myeloblastic leukemia (AML-M0) exhibiting tetraploidy and erythrophagocytosis. The karyotype was 46,XX[2]/92,XXXX[18]. Bone marrow aspirate smears showed large and prominent nuclei, with erythrophagocytosis in leukemic cells. Fluorescence in situ hybridization using RUNX1 dual color break probes detected four fusion signals, accounting for 95 % (190/200), in one interphase nucleus. The mutations of TP53 and the fusion genes RUNX1/ETO, CBFß/MYH11, and PML/RARα were all negative. This patient showed a poor response to chemotherapy, and died 66 days after the onset. To our knowledge, this is the first reported case of AML-M0 with tetraploidy and erythrophagocytosis and without additional chromosome aberrations. This case of tetraploid AML with poor prognosis suggests that further biological study of more cases of tetraploid AML will be of great importance in improving the understanding and prognosis of this tetraploid AML.

[Expression of WT1 gene and its isomer ratio changes during phorbol ester induced differentiation of K562 cell line].

OBJECTIVE: To explore the changes in expression of WT1 gene and ration of its isomers during phorbol ester (TPA) induced differentiation of leukemia cell line K562 by fluorescence quantitative RT-PCR and analysis the relationship between different isomers and hematogenic cell differentiation. METHODS: The degree of cellular maturation were verified by NBT reduction test and immunophenotyping. Expression of WT1 gene was determined by fluorescence quantitative RT-PCR during differentiation of K562 cell line. The relative ratio of the four splicing variants WT1 ( + / + ), WT1 ( + / - ), WT1 ( - / + ), WT1 ( - / - ) were calculated. RESULTS: During the differentiation of K562 cell, the NBT reduction rate and the CD9 positive rate both increased significantly (P < 0. 05). The expression of WT1 gene decreased immediately to (1.67 +/- 0.45) x 10(-3) from (4.67 +/- 1.11) x 10(-3), and then increased again to (4.64 +/- 1.53) x 10(-3) at 96 hours. The ratio of WT1 ( + / + ) was decreased gradually, from 0 hour (39.65 +/- 19.46)% to 96 hour (15.25 +/- 7.27)%. While the ratio of WT1( - / - ) was increased, from 0 hour (15.38 +/- 11.34)%, to 96 hour (37.60 +/- 11.90)%. The other two isomers ratios did not change significantly. CONCLUSION: During the TPA induced differentiation of K562 cell, there are two high expression levels of WT1 gene. Before differentiation, the majority is WT1 ( + / + ), and after differentiation, is WT1 ( - / - ). It indicates that WT1 gene may activate or inhibit cell differentiation by regulating the ratio of its four splicing variants.