Novel Splicing Variants in the ARR3 Gene Cause the Female-Limited Early-Onset High Myopia.

Purpose: Variants in the ARR3 gene have been linked to early-onset high myopia (eoHM) with a unique X-linked female-limited inheritance. However, the clinical validity of this gene-disease association has not been systematically evaluated. Methods: We identified two Chinese families with novel ARR3 splicing variants associated with eoHM. Minigene constructs were generated to assess the effects of the variants on splicing. We integrated previous evidence to curate the clinical validity of ARR3 and eoHM using the ClinGen framework. Results: The variants c.39+1G>A and c.100+4A>G were identified in the two families. Minigene analysis showed both variants resulted in abnormal splicing and introduction of premature termination codons. Based on genetic and experimental evidence, the ARR3-eoHM relationship was classified as "definitive." Conclusions: Our study identified two novel splicing variants of the ARR3 gene linked to eoHM and confirmed their functional validity via minigene assay. This research expanded the mutational spectrum of ARR3 and confirmed the minigene assay technique as an effective tool for understanding variant effects on splicing mechanisms.

Aberrant splicing caused by a novel KMT2A variant in Wiedemann-Steiner syndrome.

INTRODUCTION: Wiedemann-Steiner syndrome (WSS) is a rare autosomal-dominant disorder caused by KMT2A variants. The aim of this study was to characterize a novel KMT2A variant in a child with WSS and demonstrate integrated diagnostic approaches. METHODS: A 3-year-old female with developmental delay, distinctive facial features, and anal fistula underwent whole exome sequencing (WES). RNA analysis was performed to assess splicing effects caused by a novel variant. RESULTS: WES identified novel heterozygous KMT2A c.5664+6T>C variant initially classified as a variant of uncertain significance. RNA analysis provided evidence of aberrant splicing (exon 20 skipping), allowing reclassification to likely pathogenic. The patient exhibited typical WSS features along with a potential novel finding of anal fistula. CONCLUSION: This report describes a novel non-canonical splice site variant in KMT2A associated with WSS. RNA analysis was critical for variant reclassification. Detailed phenotypic evaluation revealed common and expanded WSS manifestations. This case highlights the importance of combining clinical assessment, DNA testing, and RNA functional assays for the diagnosis of rare genetic disorders.

Relationship of the levels of reactive oxygen species in the fertilization medium with the outcome of in vitro fertilization following brief incubation.

Embryo selection in in vitro fertilization-embryo transfer (IVF-ET) mostly relies on morphological assessment using a conventional microscope or the time-lapse monitoring system, which is not comprehensive. Inappropriate levels of reactive oxygen species (ROS) in the fertilization medium may cause damage to gametes, eventually leading to adverse IVF outcomes. The present study aimed to identify the optimal oxidation-reduction level in the fertilization medium for IVF outcomes by measuring the static oxidation-reduction potential (sORP) using a highly accurate and sensitive MiOXSYS system. A total of 136 patients undergoing IVF following brief incubation were divided equally into 4 groups in this prospective cohort study. The sORP value in the fertilization medium was detected using the MiOXSYS system, and its relationship with IVF outcomes was analyzed. The primary outcome was pregnancy outcomes, including live birth rate (LBR), clinical pregnancy rate (CPR), biochemical pregnancy rate (BPR), and implantation rate (IR). The secondary outcome was embryo quality, including fertilization rate (FR), cleavage rate (CR), available embryo rate (AER), and good-quality embryo rate (GQER). Group II (sORP: 228.7-235.3 mV) showed a higher LBR, CPR, BPR, and IR compared with Group III (sORP: 235.4-242.7 mV), presented as follows: LBR (32.0% for Group II vs 3.6% for Group III, P = 0.033), CPR (32.0% for Group II vs 3.6% for Group III, P = 0.033), BPR (36.0% for Group II vs 3.6% for Group III, P = 0.019), and IR (31.3% for Group II vs 2.7% for Group III, P = 0.003). The FR in Groups I and II had lower significant differences compared with that in Groups III and IV (71.7% and 70.3% for Groups I and II vs 83.5% and 80.4% for Groups III and IV, P = 0.000). The GQER in Group I to Group IV was 32.7%, 37.4%, 26.5%, and 33.3%, respectively (P = 0.056). This study indicated that the sORP value in the fertilization medium might be a potential indicator of embryo quality and pregnancy outcome.

Analysis of Cross-Cultural Communication in English Subjects and the Realization of Deep Learning Teaching.

In subject teaching, subject characteristics are the logical starting point for teaching development, and a deep understanding of subject characteristics is the basis for effective teaching. In practice, due to ignoring the cross-cultural understanding of middle school English subjects, there has been a long-term dilemma of "emphasizing knowledge and neglecting culture," and overemphasis on the instrumental nature of middle school English has caused middle school English teaching to lose cultural self-cultivation and obscured the due education human value. Under the background of globalization and diversification, it is more and more important to develop students' cross-cultural awareness. How to realize cross-culturalism in middle school English teaching has become an important subject of teaching reform and development. From the perspective of English subject, this research constructs a scientific and implementable English listening and speaking teaching mode that promotes students' in-depth learning, provides specific and operational teaching implementation plans for English subject teachers in front-line teaching, and improves classroom teaching. It can promote students' construction of the meaning of language knowledge, stimulate their learning motivation, and finally achieve the common development of teachers and students.

The Construction of English Smart Classroom Teaching Mode Based on Deep Learning.

Deep learning has an increasingly far-reaching impact on classroom teaching and is an important trend driving the application of educational technology in schools. In the traditional lecture-style teaching process, students are mostly in a passive listening and memorizing state. Simple memorization and repeated training have a certain hindering effect on promoting the transfer and application of the learner's knowledge, and it is not suitable to exert the learner's subjectivity. This research uses the current rapidly developing wireless communication technology to transmit data to the English teaching management platform, so as to realize the information exchange between the English classroom monitoring terminal and the English teaching management platform. The monitoring terminal of the system is mainly responsible for data collection of information, such as student campus card information, the location of the monitoring terminal, and terminal equipment parameters, and uses wireless communication information technology to upload it to the English teaching management platform according to the communication protocol agreed between the terminal and the platform, and the English teaching management platform can issue instructions to the monitoring terminal, so as to realize the control and management functions of the monitoring terminal. The design of the English teaching management platform of this system is a Web system designed based on B/S architecture. The interface of the system is diverse, and English teachers can easily view the monitoring data on the platform through this system. The main function of the English teaching management platform is to receive the data collected from the monitoring terminal, parse the information, and display the processing results to the English teacher in the form of a page. In order to facilitate the storage of data, MySQL database is used for the background data storage of the English teaching management platform. Through the design of the hardware terminal module and the development of the English teaching management platform, a deep learning-based English smart classroom management prototype system is realized.

Association between ambient air pollution and pregnancy outcomes in patients undergoing in vitro fertilization in Shanghai, China: A retrospective cohort study.

BACKGROUND: The effects of ambient air pollutants on adverse pregnancy outcomes have been reported. However, studies about air pollutants exposure and pregnancy outcomes in patients undergoing IVF were limited and inconclusive. To date Shanghai has been the only city in China to implement a compulsory single embryo transfer policy for all patients undergoing their first embryo transfer procedure effective from January 2019. We aimed to investigate the associations between exposure to ambient air pollutants and biochemical pregnancy and live births, and to identify potential vulnerability characteristics of patients undergoing IVF in Shanghai, China. METHODS: A retrospective cohort study was conducted on 2766 infertile patients aged ≤ 45 years who underwent first fresh or frozen-thawed cleavage stage embryo transfer in the Shanghai First Maternity and Infant Hospital during April 2016 and December 2019. Daily average ambient levels of six air pollutants (PM2.5, PM10, NO2, SO2, CO and O3 max-8h) were obtained from fixed air monitors located in closest proximity to patients' residences. The cumulative average level was calculated during three different exposure periods (period1: three months before oocyte retrieval to serum hCG test; period 2: from serum hCG test to live birth outcome; period 3: from three months before oocyte retrieval to live birth). Multiple logistic regression model was performed to investigate associations between exposure to ambient air pollutants and pregnancy outcomes. Stratified analyses were conducted to explore the potential effects modifier. RESULTS: The biochemical pregnancy rate and live birth rate were 54.2% and 36.4%, respectively. The ambient NO2 exposure was significantly associated with a 14% lower pregnancy rate during period 1 (aOR = 0.86, 95%CI: 0.75-0.99). The ambient PM10 was related to significantly increased risk of lowering live birth rate among the patients during period 3 [aOR = 0.88(0.79-0.99)]. Stratified analysis showed that ambient PM10 was also significantly associated with a reduced pregnancy rate (aOR = 0.82, 95% CI: 0.69-0.97) in patients who underwent single embryo transfer during period 1. Subjects who underwent single embryo transfer also had a decreased likelihood of a live birth when exposed to ambient SO2 and O3 during period 3 [aOR = 0.74(0.57-0.95), and 0.92 (0.83-0.98), respectively]. Moreover, O3 exposure was associated with decreased live birth rates in patients living in non-urban areas. Sensitivity analyses indicated robust negative association between PM10 exposure and live birth outcomes. CONCLUSIONS: Our study suggested that exposure to ambient air pollutants, in particular NO2 and PM10, was associated with an increased risk of lower rates of pregnancy and live birth respectively in patients undergoing IVF. Stratified analyses indicated that ambient SO2 and O3 levels were related to adverse pregnancy outcomes in some subgroups of IVF patients in this study. Notably, patients who underwent single embryo transfer were more susceptible to ambient air pollution exposure. Thus, prospective cohort studies are needed to investigate the underlying mechanisms and the susceptibility windows for women undergoing IVF treatment.

Noise-suppressing channel allocation in dynamic DWDM-QKD networks using LightGBM.

Integrating quantum key distribution (QKD) with existing optical networks is highly desired to reduce the deployment costs and achieve efficient resource utilization, and some point-to-point transmitting experiments have verified its feasibility. Nevertheless, there are still many problems in the realistic scenario where QKD coexists with dynamic data traffics. On the one hand, the conventional static channel allocation schemes cannot guarantee the quality of quantum channels in the presence of the time-varying noises. On the other hand, considering the complex noise generation caused by dynamic classical data traffics with variable characters, it is challenging to achieve online high-performance quantum channel assignments. To address these problems, we propose a machine learning based noise-suppressing channel allocation (ML-NSCA) scheme. In this scheme, the LightGBM based ML framework is trained to predict the optimal channel allocations with lowest noise impacts, according to which, the quantum channels are periodically reallocated to guarantee high secure key rate. To improve the accuracy and scalability of the ML framework, we also optimize the method of feature extraction during the training process. The performance evaluation results indicate that the proposed scheme can effectively resist the dynamic noise impacts in the realistic optical networks and obtain higher secure key rate with less operation complexity than the previous schemes.

Fluorescent carbon dots derived from urine and their application for bio-imaging.

This study aims to obtain water-soluble fluorescent carbon dots (C-dots) from low-value metabolites through a simple, economical, one-step synthetic route. The urine C-dots (UCDs) and hydrothermally treated urine C-dots (HUCDs) were obtained, respectively, using straightforward Sephadex filtration method from human adults and hydrothermal reaction method. The UCDs and HUCDs emit fluorescence upon being excited with ultraviolet light with a quantum yield of 4.8% and 17.8%, respectively. TEM analysis revealed that UCDs and HUCDs had an average size of 2.5 nm and 5.5 nm, respectively. X-ray photoelectron spectroscopy (XPS) analysis showed the UCDs and HUCDs were mainly composed of carbon, oxygen and nitrogen. Fourier-transform infrared (FTIR) spectroscopy demonstrated the presence of functional groups, such as amino, hydroxyl, carboxylate and carbonyl groups onto the C-dots. The UCDs and HUCDs can be directly used for in vivo and in vitro imaging in Hela cells, Caenorhabditis elegans, onion epidermal cells and bean sprouts. The cytotoxicity study revealed that the UCDs and HUCDs were not toxic to normal rat kidney (NKR) cells with good biocompatibility. The results revealed that the C-dots derived from urine have good biocompatibility, strong fluorescence and may have potential to be a safe fluorescent probe for bio-imaging.

Experimental wavelength-space division multiplexing of quantum key distribution with classical optical communication over multicore fiber.

We demonstrate quantum key distribution (QKD) with classical signals in a seven-core fiber using dense wavelength division multiplexing. Quantum signals are transmitted in an outer core separately and intercore crosstalk (IC-XT) is the main impairment of them. In order to alleviate IC-XT, we propose a quantum-classical interleave scheme. Then the properties of IC-XT are analyzed based on the measurement results, which indicate counter-propagation is a better co-existence method than co-propagation. Finally, we perform QKD experiments in the presence of two classical channels with a channel spacing of 100 GHz between quantum channel and the nearest classical channels. The experiment results prove counter-propagation almost immune to IC-XT, which is consistent with our analysis. Also, the feasibility of the transmission over the range of metropolitan area networks is validated with our scheme.

Optimized channel allocation scheme for jointly reducing four-wave mixing and Raman scattering in the DWDM-QKD system.

Conducting quantum key distribution (QKD) through existing optical fibers together with conventional communication signals is a viable way to expand its practical application, but weak quantum signals can be severely disrupted by co-propagating classical signals. In this paper, the suppression of four-wave mixing (FWM) noise and Raman noise is considered simultaneously for the first time, to the best of our knowledge, and the joint optimized channel allocation (JOCA) scheme is proposed. In the JOCA scheme, the quantum channels and classical channels are interleaved with each other to avoid FWM noise and optimal quantum channel positions are chosen in variable conditions according to the Raman scattering spectrum. Experimental measurements of the noise photons show that the JOCA scheme can effectively reduce the impairments on quantum signals compared with the single-target schemes. Additionally, simulation results verify that the JOCA scheme can increase the secure key generation rate and transmission distance, and that it also enables the DWDM-QKD system to tolerate higher-power classical signals and more classical channels, which improve the compatibility with a high-capacity communication system.

Clinical implications of ß-catenin protein expression in breast cancer.

The objective of this study was to examine the expression and significance of ß-catenin in the diagnosis and prognosis of breast cancer. Overall, 241 patients with histologically confirmed breast cancer who had undergone radical surgery were enrolled in this study. ß-catenin protein expression in breast cancer samples was evaluated by immunohistochemistry. ß-catenin was expressed in Nuclei/Plasma of the samples from 41 patients. ß-catenin protein expression correlated with the histological grade of the tumor (P<0.05) and Ki-67 labeling (P<0.01). Survival analysis showed that ß-catenin expression negatively correlated with breast cancer-specific survival. Our results showed prominent expression of ß-catenin in breast cancer and strongly implicate the ß-catenin in tumor promotion.