Search

There are a series of challenges in microgrid transactions, and blockchain technology holds the promise of addressing these challenges. However, with the increasing number of users in microgrid transactions, existing blockchain systems may struggle to meet the growing demands for transactions. Therefore, this paper proposes an efficient and secure blockchain consensus algorithm designed to meet the demands of large-scale microgrid electricity transactions. The algorithm begins by utilizing a Spectral clustering algorithm to partition the blockchain network into different lower-level consensus set based on the transaction characteristics of nodes. Subsequently, a dual-layer consensus process is employed to enhance the efficiency of consensus. Additionally, we have designed a secure consensus set leader election strategy to promptly identify leaders with excellent performance. Finally, we have introduced an authentication method that combines zero-knowledge proofs and key sharing to further mitigate the risk of malicious nodes participating in the consensus. Theoretical analysis indicates that our proposed consensus algorithm, incorporating multiple layers of security measures, effectively withstands blockchain attacks such as denial of service. Simulation experiment results demonstrate that our algorithm outperforms similar blockchain algorithms significantly in terms of communication overhead, consensus latency, and throughput. [ABSTRACT FROM AUTHOR]

Contributed to the development of next-generation sequencing (NGS) technology, more and more chromosomally mosaic and aneuploid embryos are discovered during the preimplantation genetic testing for aneuploidy (PGT-A) cycles. Because mosaicism and aneuploidy are routine phenomena throughout human pre- and post-implantation development. The benefit of implanting such mosaicism or aneuploidies detected by precise NGS remains controversial. This study aimed to investigate chromosomal concordance between babies produced by PGT-A and trophectoderm (TE) biopsies, and whether precise NGS resolution would reduce the development of an abnormal embryo in PGT cycles. Peripheral blood samples from 17 PGT-A babies were collected to compare with TE biopsy results at different NGS resolutions. 16 euploid embryos diagnosed by 10 Mb resolution developed into 16 healthy babies with normal copy number variations (CNVs). One mosaic embryo diagnosed by both 10 Mb and 4 Mb resolution also produced a euploid baby finally. Among them, four euploid embryos diagnosed by 10 Mb NGS, showed segmental aneuploidy at 4 Mb NGS resolution. Four of them developed into euploid babies with normal CNVs finally. NGS at 10 Mb resolution is accurate enough to diagnose viable embryos. A more precise NGS resolution (e.g., 4 Mb resolution) results in discard of some potentially viable embryos. It is suggested to analyze the TE biopsy at both 10 Mb and 4 Mb resolutions to identify embryos with adverse chromosomal aberrations, but using 10 Mb resolution for guide transfer to increase a development chance of an embryo. Trial registration: www.ClinicalTrials.gov , identifier ChiCTR2100042522. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the efficacy and safety of short-term insemination and early-rescue intracytoplasmic sperm injection (ICSI), an approach that rescued oocytes with unclear second polar body 6 h after initial insemination by ICSI (early R-ICSI) to avoid total or near-total fertilization failure in conventional in vitro fertilization (IVF). Methods: We performed a retrospective study in 16,769 patients (short-term IVF, n = 12,094; ICSI, n = 3452; early R-ICSI, n = 1223) who received IVF/ICSI treatment in our hospital from January 2009 to October 2018. Fertilization and clinical outcomes were compared among those three groups. Results: When considering the R-ICSI embryos in the early R-ICSI group independently, the rates of fertilization and day-3 cleaved embryos in 2PN oocytes were comparable, the rates of fertilization (2PN) and high-quality embryos were lower, whereas the multi-PN fertilization rate (3.27%) was significantly higher than the ICSI group (1.26%). The difference of clinical pregnancy rate between the part of transferred R-ICSI embryos (40.81%) and the ICSI group (44.73%) remained nonsignificant. Furthermore, the rate of congenital birth defects in the early R-ICSI group (0.99%) was not significantly different from those in the short-term IVF (0.76%) and ICSI groups (1.07%). Conclusion: Despite the multi-PN fertilization rate, our study highlights early R-ICSI as a safe and effective alternative in assisted reproduction to decrease complete IVF fertilization failure and reduce ICSI utilization. Additional large amount and long-term follow-up studies are needed to further validate the use of early R-ICSI. [ABSTRACT FROM AUTHOR]

Security surveillance system plays an important role in the society. However, how to securely send the sensitive information from the surveillance node to the server is a critical issue which should be well addressed. In this paper, to develop a secure communication scheme applied between the surveillance camera and the server, we propose the important and desirable security and privacy features that should be achieved by such systems, and present a secure scheme that can achieve the security goals. Our scheme ensures that encrypted datagrams not sent from the surveillance cameras can be filtrated by a public message filter while data and sender privacy is still well preserved for encrypted data sent from legitimated cameras. Furthermore, the server in our scheme is the only entity which can reveal the real sender given a ciphertext produced by it and give a proof to convince others the origination of that ciphertext without leaking its content. Such property enables the server to build a searchable database using the camera's identifier as index and also the message auditor to check the ciphertext and its origination stored in the database without any dispute. We provide the formal security models to define these security requirements and give formal security proofs in the random oracle model. [ABSTRACT FROM AUTHOR]

Background: Oocyte maturation arrest at metaphase I leads to fertilization failure in humans. In early embryos, the tubulin beta 8 class VIII (TUBB8) encodes a β-tubulin isotype and aids in the assembling of the human oocyte spindle. Mutations in the TUBB8 potentially interfere with human oocyte maturation—a crucial prerequisite for fertilization and subsequent embryonic development. This study aims to investigate the novel mutations in TUBB8 and their prevalence. Results: Hundred fertile women (controls) and eleven infertile women with oocyte maturation arrest were chosen for the study. A total of five TUBB8 heterozygous/homozygous mutations were found in eleven infertile females (p.A313V, p.C239W, p.R251Q, p.P358L, and p.G96R). The Exome Aggregation Consortium (ExAC), SIFT, and PolyPhen-2 analyses revealed that p. A313V has unknown pathogenicity and p.C239W, p.R251Q, p.P358L, and p.G96R have possible pathogenicity. The wild-type (WT) and four mutant gene constructs were transfected to Hela cells. The Western blot analysis indicates that the TUBB8 expression of the p.C239W, p.R251Q, and p.G96R mutations was significantly decreased than that of WT. The immunofluorescence assay showed that the Hela cells transfected with either p.C239W, p.R251Q, or p.G96R mutations exhibited the disrupted microtubule structure, revealing a significant difference in the organization of the microtubule network compared to the WT. Conclusions: We identified three novel variants and two reported variants out of 11 infertile women with oocyte metaphase I arrest. According to the present data, TUBB8 gene variants account for 31.96% of all participants (109/341) with oocyte maturation arrest. [ABSTRACT FROM AUTHOR]

We present an access control encryption (ACE) scheme which enjoys advantages over previous works in several aspects. Our scheme ensures not only compact ciphertext size but also small size of keys installed in each user in the ACE system. Besides, to the best of our knowledge, our scheme is the first implementation of ACE with decentralized sanitizers. Comparing to ACE constructions with only one sanitizer, our scheme is more secure and reliable since it does not suffer from the single point failure. Considering the security of our scheme, we present two models catering to the no-read rule and no-write rule security requirements respectively. Additionally, our extended no-write rule model allows the corruption of some sanitizers in the ACE system and thus is stronger than the one for schemes with only one sanitizer. We prove the security of our scheme under the two models. [ABSTRACT FROM AUTHOR]

Arrested cells/ cellular debris is component left in the zona pellucida after blastocyst hatching. To identify whether expelling arrested cells/cellular debris from blastocysts is a process of human embryo self-correction by eliminating abnormal cells, 21 pairs of trophectoderm (TE) biopsies and the corresponding arrested cells/cellular debris expelled from the blastocysts from July to December 2020 were collected and analyzed using next-generation sequencing (NGS). Then, the NGS results of TE biopsies and the corresponding arrested cells/cellular debris were compared. We identified that 47.6% of blastocysts (10/21) were aneuploidies and mosaicism. A total of 18 groups of arrested cells/cellular debris (85.7%) expelled from blastocysts were abnormal, including nine aneuploid embryos and nine euploid embryos. In the arrested cells/cellular debris, all the chromosomes were affected. In conclusion, mosaicism and aneuploidies are common features of early embryonic development, and the arrested cells/cellular debris expelled from blastocysts provides evidence of early embryonic self-correction. [ABSTRACT FROM AUTHOR]

Preimplantation embryonic arrest is an important pathogenesis of female infertility, but little is known about the genetic factors behind this phenotype. MEI4 is an essential protein for DNA double-strand break formation during meiosis, and Mei4 knock-out female mice are viable but sterile, indicating that MEI4 plays a crucial role in reproduction. To date, MEI4 has not been found to be associated with any human reproductive diseases. Here, we identified six compound heterozygous and homozygous MEI4 variants—namely, c.293C > T, p.(Ser98Leu), c.401C > G, p.(Pro134Arg), c.391C > G, p.(Pro131Ala), c.914A > T, p.(Tyr305Phe), c.908C > G, p.(Ala303Gly), and c.899A > T, p.(Gln300Leu)—in four independent families that were responsible for female infertility mainly characterized by preimplantation embryonic arrest. In vitro, we found that these variants reduced the interaction between MEI4 and DNA. In vivo, we generated a knock-in mouse model and demonstrated that female mice were infertile and were characterized by developmental defects during oogenesis. Our findings reveal the important roles of MEI4 in human reproduction and provide a new diagnostic marker for genetic counseling of clinical infertility patients. [ABSTRACT FROM AUTHOR]

Background: Structural rearrangements in highly repetitive heterochromatin regions can result in miscarriage or foetal malformations; however, detecting and preventing the transmission of these rearrangements has been challenging. Recently, the completion of sequencing of the complete human genome (T2T‐CHM13) has made it possible to accurately characterise structural rearrangements in these regions. We developed a method based on T2T‐CHM13 and nanopore sequencing to detect and block structural rearrangements in highly repetitive heterochromatin sequences. Methods: T2T‐CHM13‐based "Mapping Allele with Resolved Carrier Status" was performed for couples who carry structural rearrangements in heterochromatin regions. Using nanopore sequencing and the T2T‐CHM13 reference genome, the precise breakpoints of inversions and translocations close to the centromere were detected and haplotypes were constructed using flanking single‐nucleotide polymorphisms (SNPs). Haplotype linkage analysis was then performed by comparing consistent parental SNPs with embryonic SNPs to determine whether the embryos carried hereditary inversions or balanced translocations. Based on copy number variation and haplotype linkage analysis, we transplanted normal embryos, which were further verified by an amniotic fluid test. Results: To validate this approach, we used nanopore sequencing of families with inversions and reciprocal translocations close to the centromere. Using the T2T‐CHM13 reference genome, we accurately detected inversions and translocations in centromeres, constructed haplotypes and prevented the transmission of structural rearrangements in the offspring. Conclusions: This study represents the first successful application of T2T‐CHM13 in human reproduction and provides a feasible protocol for detecting and preventing the transmission of structural rearrangements of heterochromatin in embryos. [ABSTRACT FROM AUTHOR]

Background: TUBB8, a crucial gene encoding microtubule protein, plays a pivotal role in cellular processes. Deleterious TUBB8 variants have been shown to significantly hinder oocyte maturation. In this study, we conducted an in vitro investigation using TUBB8 mutant mouse oocytes to elucidate the pathogenic mechanisms of TUBB8 variants in oocyte nuclear and cytoplasmic maturation. Methods: A mutant model was successfully established in mouse oocytes via microinjection to further investigate the effects of four novel discovered TUBB8 mutations on the nuclear and cytoplasmic maturation of mouse oocytes. Immunofluorescence and confocal microscopy were performed to observe the cortical polarity and spindle and of mutant oocytes. Active mitochondrial staining was performed to analyze mitochondrial distribution patterns. Endoplasmic reticulum and Ca2+ staining were conducted to assess ER distribution and cytoplasmic calcium ion concentration in oocytes. Results: In mouse oocytes, TUBB8 variants (p.A313V, p.C239W, p.R251Q, and p.G96R) resulted in a reduction of the first polar body extrusion rate, disruption of spindle assembly, and abnormal chromosome distribution. Additionally, these variants induced oocyte organelle abnormalities, including anomalies in mitochondrial redistribution and endoplasmic reticulum stress compared to the wild-type. Conclusion: Deleterious TUBB8 variants could disrupt microtubule function, affecting critical processes such as spindle assembly, chromosome distribution, and organelle rearrangement during oocyte meiosis. These disruptions culminate in compromised nuclear-cytoplasmic maturation, consequently giving rise to oocyte maturation defects. [ABSTRACT FROM AUTHOR]

Background: The study investigated whether specific ultrasonographically observed endometrial features (including endometrium type and thickness) were linked to ectopic pregnancy after stimulated cycles with fresh embryo transfer. Method: Of 6246 pregnancy cycles after fresh embryo transfer, 6076 resulted in intrauterine pregnancy and 170 in ectopic pregnancy. The primary outcome of the study was ectopic pregnancy, with the main variables being endometrium type and endometrial thickness. Univariate and subsequent multiple-stepwise logistic regression analyses were used to identify the risk factors of ectopic pregnancy. Results: 1. Compared with patients with an endometrial thickness ≥ 8 mm, the adjusted odds ratio for those with an endometrial thickness < 8 mm was 3.368 (P < 0.001). The adjusted odds ratio for women with a type-C endometrium was 1.897 (P = 0.019) compared with non-type C. 2. A larger dose of gonadotropin used during controlled ovarian hyperstimulation was a protective factor against ectopic pregnancy (P = 0.008). 3. The GnRH antagonist protocol (P = 0.007) was a risk factor for ectopic pregnancy, compared with the use of GnRH agonists. Conclusion: (1) An endometrial thickness < 8 mm coupled with a type C endometrium significantly increased the risk of ectopic pregnancy after fresh embryo transfer. (2) A thin endometrial thickness and a type C endometrium could be further related to an abnormal endometrial receptivity/peristaltic wave. (3) Patients at a high risk of ectopic pregnancy should therefore be given special attention, with early diagnosis during the peri-transplantation period may assist in the prevention of ectopic pregnancy. [ABSTRACT FROM AUTHOR]

A f = 162 . 5 MHz superconducting half-wave resonator (HWR) with β = 0 . 12 is one of the four superconducting cavities being developed for the heavy ion linac of the Rare Isotope Science Project (RISP). The linac will accelerate various ions ranging from proton to uranium with beam power of about 400 kW. In particular, the HWR’s will accelerate the ion beam in low–medium energy range, i.e., from 1.6 to 18 MeV for the case of uranium. In this paper, we describe design, fabrication, surface treatment, and vertical test of the 1st prototype of the cavity in detail. We also discuss some issues on the performance enhancement of the cavity. The Q 0 values at 2 K surpassed the target performance, Q 0 = 1 . 1 × 1 0 9 at E a c c = 6 . 3 MV ∕ m . [ABSTRACT FROM AUTHOR]

Offshore wind power generation has been widely applied. Generally, the offshore wind farms are far from land. Thus, maintenance is inconvenient and the costs for offshore wind power conversion systems are high. Several offshore wind power converter units are parallel connected to meet power capacity and redundancy requirements. However, operating reliability is easily affected by mistriggered switches from complex electromagnetic interference and sudden drops in output current can occur when the inverter modules switch directly. This paper studies high-reliability operation modes and a swapping strategy for offshore wind power converters to address these issues. Different operating patterns are defined based on the output power of the system. By enabling the power switches of the inverter bridges in an interleaved manner, the working patterns are reconstructed. The short-circuited current is suppressed in the power switches caused by the shoot-through of DC-link capacitors. Moreover, the power switches used in different operating modes are activated synchronously and deactivated asynchronously with the mode-swapping signals to optimize the swapping transitions. Finally, the effectiveness is validated on an experimental platform using dual active neutral-point-clamped inverters connected in parallel. [ABSTRACT FROM AUTHOR]

Background: Balanced reciprocal translocation (BRT) is one of the most common chromosomal abnormalities that causes infertility, recurrent miscarriage, and birth defects. Preimplantation genetic testing (PGT) is widely used to select euploid embryos for BRT carriers to increase the chance of a healthy live birth. Several strategies can be used to distinguish reciprocal translocation carrier embryos from those with a normal karyotype; however, these techniques are time-consuming and difficult to implement in clinical laboratories. In this study, nanopore sequencing was performed in two reciprocal translocation carriers, and the results were validated using the next-generation sequencing-based method named, "Mapping Allele with Resolved Carrier Status" (MaReCs). Results: The translocation breakpoints in both reciprocal translocation carriers were accurately identified by nanopore sequencing and were in accordance with the results obtained using MaReCs. More than one euploid non-balanced translocation carrier embryo was identified in both patients. Amniocentesis results revealed normal karyotypes, consistent with the findings by MaReCs and nanopore sequencing. Conclusion: Our results suggest that nanopore sequencing is a powerful strategy for accurately distinguishing non-translocation embryos from translocation carrier embryos and precisely localizing translocation breakpoints, which is essential for PGT and aids in reducing the propagation of reciprocal translocation in the population. [ABSTRACT FROM AUTHOR]

The Internet of Things (IoT) and cloud technologies have significantly facilitated healthcare. In such a context, medical data are collected by the terminals from the patients, manipulated, and stored on the cloud by hospitals (doctors). This brings asymmetry problems in medical data access control, processing, and storage between doctors and patients, which results in medical data sharing face many challenges such as privacy leakage and malicious feedback from cloud servers on queries. To solve these asymmetry problems, this paper proposes a medical data sharing scheme with cloud-chain cooperation and policy fusion in the IoT. Regarding asymmetrical access control rights, a conflict resolution and fusion algorithm that enables co-authorization of medical data by the doctor and the patient is introduced. To balance the symmetry of medical data storage and processing, a cloud-chain cooperation ciphertext retrieval method is proposed by means of two-stage joint searching from cloud servers and the blockchain, which can not only detect malicious medical data feedback from cloud servers, but also improve the data search efficiency. The security analysis showed that this scheme satisfies the confidentiality and verifiability of the retrieved information, and the feasibility of the proposed scheme was demonstrated through experiments. [ABSTRACT FROM AUTHOR]

Background: It has been proved that mutations in the PADI6 gene can cause early embryo arrest. This study describes a newly discovered mutation in PADI6 that expands the genetic spectrum of early embryo arrest. Methods: Peripheral blood of a patient diagnosed with early embryo arrest was collected for whole-exome sequencing. Sanger sequencing was performed to confirm this mutation. The effects of the variant were investigated in human embryonic kidney 293T (HEK293T) cells using western blotting, real-time quantitative polymerase chain reaction, and immunofluorescence. Results: A novel homozygous mutation in PADI6 was identified in the proband. The patient carried a frameshift insertion mutation c.558dupA (p.Thr187Asnfs*48), which was located in the protein arginine deiminase middle domain. The variant destroyed PADI6 protein expression and reduced PADI6 mRNA expression in HEK293T cells. Conclusions: The newly identified mutation in PADI6 accounts for early embryo arrest. It expands the spectrum of genetic causes and phenotypes of infertility in humans. These findings also provide an additional possible diagnostic marker for patients with recurrent in vitro fertilization/intracytoplasmic sperm injection failure. Plain Language Summary: Some infertile patients experience multiple in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) failure owing to recurrent early embryo arrest. However, the underlying mechanisms remain largely unknown. Due to the development of whole-exome sequencing, early embryo arrest has been confirmed as a type of Mendelian disease. This study aimed to identify the genetic cause of early embryo arrest in patients and to expand the genetic spectrum. Furthermore, it can help doctors offer better suggestions to such patients and prevent patients from suffering from multiple IVF/ICSI failures. [ABSTRACT FROM AUTHOR]

Are there associations between dyslipidaemia and pregnancy outcomes in the first complete cycle of IVF/intracytoplasmic sperm injection (ICSI)? This long-term, retrospective real-world analysis involved 5030 infertile women who underwent a first complete IVF/ICSI cycle between January 2015 and October 2020. They were categorized into dyslipidaemia (n = 1903) and control (n = 3127) groups according to serum lipid concentrations before ovarian stimulation. Propensity score matching and multivariable logistic regression were used to control for confounding variables. In the raw cohort, women with dyslipidaemia had a significantly increased late miscarriage rate (P = 0.039), decreased term birth rate (P = 0.002) and decreased live birth rate (P = 0.005) compared with non-dyslipidaemic women. In the propensity score-matched cohort, the term birth rate (P = 0.038) and live birth rate (P = 0.044) were significantly lower in the dyslipidaemia group (n = 1686) than the controls (n = 1686). Multivariable logistic regression indicated that infertile women with dyslipidaemia (P = 0.026) and elevated serum total cholesterol concentrations (total cholesterol ≥5.20 mmol/l; P = 0.028) were significantly less likely to have a live birth. Rates of late miscarriage (P = 0.027), term birth (P = 0.003) and live birth (P = 0.010) differed significantly among women with normal, borderline increased and increased serum lipid concentrations. Compared with controls, women with increased serum lipid concentrations had a significantly higher late miscarriage rate, lower term birth rate and lower live birth rate. Women with increased serum lipid concentrations were significantly less likely than controls to have a live birth. Dyslipidaemia, total cholesterol ≥5.20 mmol/l and degrees of elevated serum lipid concentrations are negatively associated with live birth rate in the first complete IVF/ICSI cycle in infertile women. [ABSTRACT FROM AUTHOR]

Background: Window of implantation (WOI) displacement is one of the endometrial origins of embryo implantation failure, especially repeated implantation failure (RIF). An accurate prediction tool for endometrial receptivity (ER) is extraordinarily needed to precisely guide successful embryo implantation. We aimed to establish an RNA-Seq-based endometrial receptivity test (rsERT) tool using transcriptomic biomarkers and to evaluate the benefit of personalized embryo transfer (pET) guided by this tool in patients with RIF.Methods: This was a two-phase strategy comprising tool establishment with retrospective data and benefit evaluation with a prospective, nonrandomized controlled trial. In the first phase, rsERT was established by sequencing and analyzing the RNA of endometrial tissues from 50 IVF patients with normal WOI timing. In the second phase, 142 patients with RIF were recruited and grouped by patient self-selection (experimental group, n = 56; control group, n = 86). pET guided by rsERT was performed in the experimental group and conventional ET in the control group.Results: The rsERT, comprising 175 biomarker genes, showed an average accuracy of 98.4% by using tenfold cross-validation. The intrauterine pregnancy rate (IPR) of the experimental group (50.0%) was significantly improved compared to that (23.7%) of the control group (RR, 2.107; 95% CI 1.159 to 3.830; P = 0.017) when transferring day-3 embryos. Although not significantly different, the IPR of the experimental group (63.6%) was still 20 percentage points higher than that (40.7%) of the control group (RR, 1.562; 95% CI 0.898 to 2.718; P = 0.111) when transferring blastocysts.Conclusions: The rsERT was developed to accurately predict the WOI period and significantly improve the pregnancy outcomes of patients with RIF, indicating the clinical potential of rsERT-guided pET. Trial registration Chinese Clinical Trial Registry: ChiCTR-DDD-17013375. Registered 14 November 2017, http://www.chictr.org.cn/index.aspx. [ABSTRACT FROM AUTHOR]

Is the novel homozygous nonsense variant of AK7 associated with multiple morphological abnormalities of the sperm flagella (MMAF), a specific type of oligoasthenoteratozoospermia leading to male infertility? Whole-exome sequencing and Sanger sequencing were performed to identify potential gene variants. Immunoblotting and immunofluorescence were applied to confirm the relationship between mutated genes and disease phenotypes. The concentration of reactive oxygen species and the rate of apoptosis were measured to evaluate the mitochondrial function of spermatozoa. Transmission electron microscopy and scanning electron microscopy were employed to observe sperm ultrastructure. A novel homozygous nonsense variant of AK7 , c.1153A>T (p. Lys385*), was identified in two infertile siblings with asthenoteratozoospermia through whole-exome sequencing. Both immunoblotting and immunofluorescence assays showed practically complete absence of AK7 in the patient's spermatozoa. Additionally, the individual with the novel AK7 variant exhibited a phenotype characterized by severe oxidative stress and apoptosis caused by mitochondrial metabolic dysfunction of spermatozoa. Notably, remarkable flagellar defects with multiple axonemes in uniflagellate spermatozoa, accompanied by mitochondrial vacuolization, were observed; this has not been reported previously in patients with other AK7 variants. This study found that a novel identified homozygous nonsense variant of AK7 may be associated with MMAF-related asthenoteratozoospermia. The observed functional associations between mitochondria and sperm flagellar assembly provide evidence for potential mutual regulation between AK7 and flagella-associated proteins during spermatogenesis. [ABSTRACT FROM AUTHOR]