Summary
Globozoospermia and acephalic spermatozoa are two rare sperm head anomalies associated with male infertility. Combination of the two phenotypes in the same patient is extremely rare, so the ...underlying pathogenesis of this disorder remains unclear. Here, we report a 35‐year‐old infertile male, who presented with 30% of sperm‐lacked heads and 69% of sperm round‐headed or small‐headed with neck thickening in his ejaculate. Subsequent whole‐exome sequencing (WES) analysis identified compound heterozygous variants within the DNAH6 gene. DNAH6 is a testis‐specific‐expressed protein that was localised to the neck region in the spermatozoa of normal control; however, immunofluorescent staining failed to detect DNAH6 protein in the patient's spermatozoa. Quantitative real‐time PCR analysis also showed the complete absence of DNAH6 mRNA in the patient's spermatozoa. Moreover, two cycles of in vitro fertilisation (IVF)‐assisted reproduction were carried out, but pregnancy was not achieved after embryo transfer. Therefore, rare sequence variants in DNAH6 might be susceptibility risks for human sperm head anomaly.
Acephalic spermatozoa is a rare teratozoospermia associated with male infertility. However, the pathogenesis of this disorder remains unclear. Here, we report a 27 years old infertile male from a ...consanguineous family, who presented with 99% headless sperm in his ejaculate. Electron microscopic and immunofluorescence analysis suggested breakage at the midpiece of the patient's sperm cells. Subsequent whole‐exome sequencing analysis identified a homozygous deletion within TSGA10 (c.211delG; p.A71Hfs*12), which resulted in the production of truncated TSGA10 protein. TSGA10 is a testis‐specific protein that localized to the midpiece in the spermatozoa of a normal control; however, immunostaining failed to detect TSGA10 protein in the patient's sperm. Western blot analysis also showed complete absence of TSGA10 protein in the patient. One cycle of in vitro fertilization‐assisted reproduction was conducted, but pregnancy was not achieved after embryo transfer, possibly due to poor embryo quality. Therefore, we speculate that the presence of rare sequence variants within TSGA10 may be associated with acephalic spermatozoa in humans.
Acephalic spermatozoa due to biallelic TSGA10 mutation.
Trapped ions are one of the leading platforms in quantum information science. For quantum computing with large circuit depth and quantum simulation with long evolution time, it is of crucial ...importance to cool large ion crystals at runtime without affecting the internal states of the computational qubits, thus the necessity of sympathetic cooling. Here, we report multi-ion sympathetic cooling on a long ion chain using a narrow cooling beam focused on two adjacent ions, and optimize the choice of the cooling ions according to the collective oscillation modes of the chain. We show that, by cooling a small fraction of ions, cooling effects close to the global Doppler cooling limit can be achieved. This experiment therefore demonstrates an important enabling step for quantum information processing with large ion crystals.
Among all subtypes of breast cancer, triple-negative breast cancer has a relatively high relapse rate and poor outcome after standard treatment. Effective strategies to reduce the risk of relapse and ...death are needed.
To evaluate the efficacy and adverse effects of low-dose capecitabine maintenance after standard adjuvant chemotherapy in early-stage triple-negative breast cancer.
Randomized clinical trial conducted at 13 academic centers and clinical sites in China from April 2010 to December 2016 and final date of follow-up was April 30, 2020. Patients (n = 443) had early-stage triple-negative breast cancer and had completed standard adjuvant chemotherapy.
Eligible patients were randomized 1:1 to receive capecitabine (n = 222) at a dose of 650 mg/m2 twice a day by mouth for 1 year without interruption or to observation (n = 221) after completion of standard adjuvant chemotherapy.
The primary end point was disease-free survival. Secondary end points included distant disease-free survival, overall survival, locoregional recurrence-free survival, and adverse events.
Among 443 women who were randomized, 434 were included in the full analysis set (mean SD age, 46 9.9 years; T1/T2 stage, 93.1%; node-negative, 61.8%) (98.0% completed the trial). After a median follow-up of 61 months (interquartile range, 44-82), 94 events were observed, including 38 events (37 recurrences and 32 deaths) in the capecitabine group and 56 events (56 recurrences and 40 deaths) in the observation group. The estimated 5-year disease-free survival was 82.8% in the capecitabine group and 73.0% in the observation group (hazard ratio HR for risk of recurrence or death, 0.64 95% CI, 0.42-0.95; P = .03). In the capecitabine group vs the observation group, the estimated 5-year distant disease-free survival was 85.8% vs 75.8% (HR for risk of distant metastasis or death, 0.60 95% CI, 0.38-0.92; P = .02), the estimated 5-year overall survival was 85.5% vs 81.3% (HR for risk of death, 0.75 95% CI, 0.47-1.19; P = .22), and the estimated 5-year locoregional recurrence-free survival was 85.0% vs 80.8% (HR for risk of locoregional recurrence or death, 0.72 95% CI, 0.46-1.13; P = .15). The most common capecitabine-related adverse event was hand-foot syndrome (45.2%), with 7.7% of patients experiencing a grade 3 event.
Among women with early-stage triple-negative breast cancer who received standard adjuvant treatment, low-dose capecitabine maintenance therapy for 1 year, compared with observation, resulted in significantly improved 5-year disease-free survival.
ClinicalTrials.gov Identifier: NCT01112826.
Highlights • NRG1 protects against OGD-induced cortical neuronal apoptosis. • NRG1-mediated neuroprotection is blocked by neutralizing NRG1 and ErbB4 inhibition. • GABA receptor agonists have no ...synergistic effect with NRG1. • NRG1-mediated neuroprotection is partly blocked by GABA receptor antagonists. • The NRG1 neuroprotection against brain ischemia is abolished in PV-ErbB4−/− mice.
Asthenozoospermia (AZS) is a common cause of male infertility, characterized by abnormal reduction in the motility of ejaculated spermatozoa. Here, in a patient from a consanguineous family, we ...identified a homozygous mutation (c.G4343A, p.R1448Q) in SPAG17 by whole‐exome sequencing. The encoded protein, SPAG17, localizes to the axonemal central apparatus and is considered essential for flagellar waveform. In silico analysis revealed that R1448Q is a potential pathogenic mutation. Immunostaining and western blot assays showed that the R1448Q mutation may exert a negative effect on the steady‐state of the SPAG17 protein. Therefore, SPAG17 may be a new pathogenic gene causing AZS.
Nanocomposites using poly (vinylidene fluoride-co-hexafluoropropylene), P(VDF-HFP), as the matrix, and barium strontium titanium oxide (BST) nanoparticles as the filler were systematically studied. ...P(VDF-HFP)/BST composite films containing different amounts of BST were prepared using the solution-casting method. The dielectric constant (εr), dielectric loss (tan δ), and their frequency and temperature dependence, were characterised for the films under weak electric fields. The behaviour of the films under high electric fields was explored using polarisation-electric field (P-E) loops. The εr was found to increase from 14.1 to 42.1 as the BST content increased from 0 vol% to 40 vol%, and the Maxwell-Wagner model showed a good fit with the measured εr values, indicating that the microstructure of the fabricated nanocomposites is uniform, which can also be observed in SEM images of all P(VDF-HFP)/BST nanocomposite films. In determining the temperature (T) dependence of the εr and tan δ of the composites, P(VDF-HFP) plays a decisive role, while BST plays an influential role. As the BST content increases, the charge/discharge energy density (Ucharge/Udischarge) increases, while the breakdown strength (Eb) and charge-discharge efficiency (η) decrease. Notably, the maximal Udischarge 3.79 J/cm3 was obtained when the BST content was 20 vol% at 2100 kV/cm. In addition, from the perspective of practical application, when the applied electric field intensity is lower than 900 kV/cm or between 900 kV/cm and 2100 kV/cm, in order to obtain the maximal Udischarge, the P(VDF-HFP)/BST composite with BST content of 30 vol% or 20 vol% should be selected respectively.
A shrouded oscillating-foil turbine is proposed to augment the energy extraction performance. The oscillating foil undergoes combined plunging and pitching motion to convert the flow energy. A ...diffuser is introduced into the oscillating-foil-based turbine as the shroud. The speed-up and energy extraction performance of the turbine were assessed numerically. The effects of three cost-independent geometrical factors, namely shroud entrance width, shroud angle and streamwise distance between shroud and foil, and shroud sectional shape on energy extraction performance were investigated in detail. The optimal motion parameters for the shrouded oscillating-foil turbine were re-explored due to the altered flow field in the shroud. The results demonstrated that the maximum energy extraction efficiency of bare oscillating foil (0.336) can be augmented by 35.8% to 0.456 by appropriate arrangement of the shroud with a relative chord length of 0.8. The optimal motion parameters for the shrouded foil are slightly different from those of bare foil. The re-tuned motion parameters can further improve the efficiency to 0.47. Considering both the manufacturing cost of the shaped sections and their performance, it is more advantageous and attractive to use a flat plate as the shroud in engineering practices.
•A shrouded oscillating-foil based turbine is proposed.•The effects of cost-independent geometric factors and sectional shape are investigated.•The mechanisms of speed-up and performance improvement are analyzed.•The optimal motion parameters are readjusted for the new turbine.•Side walls of flat plate shows good performance and low-cost.
•The fast transient ignition process of impinging flames was investigated experimentally.•The fuel composition was varied from pure methane to 60% hydrogen enriched.•High speed color/schlieren images ...were taken for flame and flow field visualization.•The flow field velocity was estimated using a novel schlieren velocimetry algorithm.•The relative velocity between the flame and flow was also resolved.
The ignition characteristics of hydrogen enriched methane diffusion impinging flames are investigated experimentally. Keeping the total fuel flow rate constant, the hydrogen volume percentage is set at 40% and 60% respectively, while a pure methane flame is also involved for comparison. Two traditional optical diagnostics, high speed colour and schlieren imaging techniques have been used to tackle the fast transient ignition process with advanced digital image processing algorithms. The weak blue flame during the ignition process, which is hardly seen on the original high speed images, has been enhanced selectively to reveal the complete flame structure. The flow field velocity during the ignition process has been estimated using an optimised schlieren motion estimation method. The relative velocity between the flame and flow velocities has also been resolved and analysed. The results indicate that the flow field velocity increases with increasing hydrogen percentage. The maximum velocity detected in the test cases can be as high as over 3.5 m/s when the hydrogen volume percentage is at 60%. The techniques used in the current study are simple to set up and convenient to use, which have shown enormous potential to be applied in the experimental investigations into more complex combustion configurations.
Aims
Vibrio alginolyticus was frequently isolated from diseased farmed fish in the coaster waters of Hainan Island over the past two decades. In this study, we attempted to identify candidates of ...virulent strain‐specific DNA regions for this pathogen.
Methods and Results
Suppression subtractive hybridization (SSH) and PCR were successively performed between the typical virulent strain and avirulent strain of V. alginolyticus, in which they shared 99·54% homology of 16S rDNAs. Out of 2873 subtracted clones, nine clones were finally indicated to harbour virulent strain‐specific DNA fragments. The receivable functions of the major fragments in the nine clones were believed to encode methyl‐accepting chemotaxis protein (n = 1), type VI secretion system‐associated FHA domain protein TagH (n = 1), diguanylate cyclase (n = 1), AraC family transcriptional regulator (n = 1), ABC‐type uncharacterized transport system permease component (n = 1) and hypothetical proteins (n = 4). Two hypothetical proteins contain several disordered regions.
Conclusions
Some specific DNA regions existed in the virulent strain of V. alginolyticus, and the SSH assay could be a highly sensitive method for identifying virulent regions in pathogens.
Significance and Impact of the Study
This report is the first to describe the identification of virulent strain‐specific DNA regions in the V. alginolyticus genome, which is helpful in developing virulent strain‐specific rapid detection methods and is a pivotal precondition for clarifying the molecular virulence mechanism of V. alginolyticus.
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