Identification of the role of DAB2 and CXCL8 in uterine spiral artery remodeling in early-onset preeclampsia.

Aberrant remodeling of uterine spiral arteries (SPA) is strongly associated with the pathogenesis of early-onset preeclampsia (EOPE). However, the complexities of SPA transformation remain inadequately understood. We conducted a single-cell RNA sequencing analysis of whole placental tissues derived from patients with EOPE and their corresponding controls, identified DAB2 as a key gene of interest and explored the mechanism underlying the communication between Extravillous trophoblast cells (EVTs) and decidual vascular smooth muscle cells (dVSMC) through cell models and a placenta-decidua coculture (PDC) model in vitro. DAB2 enhanced the motility and viability of HTR-8/SVneo cells. After exposure to conditioned medium (CM) from HTR-8/SVneoshNC cells, hVSMCs exhibited a rounded morphology, indicative of dedifferentiation, while CM-HTR-8/SVneoshDAB2 cells displayed a spindle-like morphology. Furthermore, the PDC model demonstrated that CM-HTR-8/SVneoshDAB2 was less conducive to vascular remodeling. Further in-depth mechanistic investigations revealed that C-X-C motif chemokine ligand 8 (CXCL8, also known as IL8) is a pivotal regulator governing the dedifferentiation of dVSMC. DAB2 expression in EVTs is critical for orchestrating the phenotypic transition and motility of dVSMC. These processes may be intricately linked to the CXCL8/PI3K/AKT pathway, underscoring its central role in intricate SPA remodeling.

Influences of the Integrated Rice-Crayfish Farming System with Different Stocking Densities on the Paddy Soil Microbiomes.

Integrated rice-fish farming has emerged as a novel agricultural production pattern to address global food security challenges. Aiming to determine the optimal, scientifically sound, and sustainable stocking density of red claw crayfish (Cherax quadricarinatus) in an integrated rice-crayfish farming system, we employed Illumina high-throughput 16S rRNA gene sequencing to evaluate the impact of different stocking densities of red claw crayfish on the composition, diversity, function, and co-occurrence network patterns of soil bacterial communities. The high stocking density of red claw crayfish reduced the diversity and evenness of the soil bacterial community during the mid-culture stage. Proteobacteria, Actinobacteria, and Chloroflexi emerged as the most prevalent phyla throughout the experimental period. Low stocking densities initially boosted the relative abundance of Actinobacteria in the paddy soil, while high densities did so during the middle and final stages. There were 90 distinct functional groups identified across all the paddy soil samples, with chemoheterotrophy and aerobic chemoheterotrophy being the most abundant. Low stocking densities initially favored these functional groups, whereas high densities enhanced their relative abundances in the later stages of cultivation. Medium stocking density of red claw crayfish led to a more complex bacterial community during the mid- and final culture stages. The experimental period showed significant correlations with soil bacterial communities, with total nitrogen (TN) and total phosphorus (TP) concentrations emerging as primary factors contributing to the alterations in soil bacterial communities. In summary, our findings demonstrated that integrated rice-crayfish farming significantly impacted the soil microbiomes and environmental factors at varying stocking densities. Our study contributed to theoretical insights into the profound impact of integrated rice-crayfish farming with various stocking densities on bacterial communities in paddy soils.

Analysis of Video Quality Datasets via Design of Minimalistic Video Quality Models.

Blind video quality assessment (BVQA) plays an indispensable role in monitoring and improving the end-users' viewing experience in various real-world video-enabled media applications. As an experimental field, the improvements of BVQA models have been measured primarily on a few human-rated VQA datasets. Thus, it is crucial to gain a better understanding of existing VQA datasets in order to properly evaluate the current progress in BVQA. Towards this goal, we conduct a first-of-its-kind computational analysis of VQA datasets via designing minimalistic BVQA models. By minimalistic, we restrict our family of BVQA models to build only upon basic blocks: a video preprocessor (for aggressive spatiotemporal downsampling), a spatial quality analyzer, an optional temporal quality analyzer, and a quality regressor, all with the simplest possible instantiations. By comparing the quality prediction performance of different model variants on eight VQA datasets with realistic distortions, we find that nearly all datasets suffer from the easy dataset problem of varying severity, some of which even admit blind image quality assessment (BIQA) solutions. We additionally justify our claims by comparing our model generalization capabilities on these VQA datasets, and by ablating a dizzying set of BVQA design choices related to the basic building blocks. Our results cast doubt on the current progress in BVQA, and meanwhile shed light on good practices of constructing next-generation VQA datasets and models.

Sortilin-Mediated Inhibition of TREK1/2 Channels in Primary Sensory Neurons Promotes Prediabetic Neuropathic Pain.

Neuropathic pain can occur during the prediabetic stage, even in the absence of hyperglycemia. The presence of prediabetic neuropathic pain (PDNP) poses challenges to the management of individuals with prediabetes. However, the mechanisms underlying this pain remain unclear. This study aims to investigate the underlying mechanism and identify potential therapeutic targets of PDNP. A prediabetic animal model induced by a high-energy diet exhibits both mechanical allodynia and thermal hyperalgesia. Furthermore, hyperexcitability and decreased potassium currents are observed in the dorsal root ganglion (DRG) neurons of these rats. TREK1 and TREK2 channels, which belong to the two-pore-domain K+ channel (K2P) family and play an important role in controlling cellular excitability, are downregulated in DRG neurons. Moreover, this alteration is modulated by Sortilin, a molecular partner that modulates the expression of TREK1. The overexpression of Sortilin negatively affects the expression of TREK1 and TREK2, leading to increased neuronal excitability in the DRG and enhanced peripheral pain sensitivity in rats. Moreover, the downregulation of Sortilin or activation of TREK1 and TREK2 channels by genetic or pharmacological approaches can alleviate PDNP. Therefore, targeting the Sortilin-mediated TREK1/2 pathway may provide a therapeutic approach for ameliorating PDNP.

Flare: An FPGA-Based Full Precision Low Power CNN Accelerator with Reconfigurable Structure.

Convolutional neural networks (CNNs) have significantly advanced various fields; however, their computational demands and power consumption have escalated, posing challenges for deployment in low-power scenarios. To address this issue and facilitate the application of CNNs in power constrained environments, the development of dedicated CNN accelerators is crucial. Prior research has predominantly concentrated on developing low precision CNN accelerators using code generated from high-level synthesis (HLS) tools. Unfortunately, these approaches often fail to efficiently utilize the computational resources of field-programmable gate arrays (FPGAs) and do not extend well to full precision scenarios. To overcome these limitations, we integrate vector dot products to unify the convolution and fully connected layers. By treating the row vector of input feature maps as the fundamental processing unit, we balance processing latency and resource consumption while eliminating data rearrangement time. Furthermore, an accurate design space exploration (DSE) model is established to identify the optimal design points for each CNN layer, and dynamic partial reconfiguration is employed to maximize each layer's access to computational resources. Our approach is validated through the implementation of AlexNet and VGG16 on 7A100T and ZU15EG platforms, respectively. We achieve an average convolutional layer throughput of 28.985 GOP/s and 246.711 GOP/s for full precision. Notably, the proposed accelerator demonstrates remarkable power efficiency, with a maximum improvement of 23.989 and 15.376 times compared to current state-of-the-art FPGA implementations.

Light-Initiated Imprinted Membrane-Based Biomimetic SERS Sensor toward Selective Detection of Trace MC-LR.

Microcystin-LR (MC-LR) is a severe threat to human and animal health; thus, monitoring it in the environment is essential, especially in water quality protections. Herein, in this work, we synthesize PVDF/CNT/Ag molecular imprinted membranes (PCA-MIMs) via an innovative combination of surface-enhanced Raman spectroscopy (SERS) detection, membrane separation, and molecular-imprinted technique toward the analysis of MC-LR in water. In particular, a light-initiated imprint is employed to protect the chemical structure of the MC-LR molecules. Furthermore, in order to ensure the detection sensitivity, the SERS substrates are combined with the membrane via the assistance of magnetism. The effect of synthesis conditions on the SERS sensitivity was investigated in detail. It is demonstrated from the characteristic results that the PCA-MIMs present high sensitivity to the MC-LR molecules with excellent selectivity against the interfere molecules. Results clearly show that the as-prepared PCA-MIMs hold great potential applications to detect trace MC-LR for the protection of water quality.

Crocus genome reveals the evolutionary origin of crocin biosynthesis.

Crocus sativus (saffron) is a globally autumn-flowering plant, and its stigmas are the most expensive spice and valuable herb medicine. Crocus specialized metabolites, crocins, are biosynthesized in distant species, Gardenia (eudicot) and Crocus (monocot), and the evolution of crocin biosynthesis remains poorly understood. With the chromosome-level Crocus genome assembly, we revealed that two rounds of lineage-specific whole genome triplication occurred, contributing important roles in the production of carotenoids and apocarotenoids. According to the kingdom-wide identification, phylogenetic analysis, and functional assays of carotenoid cleavage dioxygenases (CCDs), we deduced that the duplication, site positive selection, and neofunctionalization of Crocus-specific CCD2 from CCD1 members are responsible for the crocin biosynthesis. In addition, site mutation of CsCCD2 revealed the key amino acids, including I143, L146, R161, E181, T259, and S292 related to the catalytic activity of zeaxanthin cleavage. Our study provides important insights into the origin and evolution of plant specialized metabolites, which are derived by duplication events of biosynthetic genes.

Exploring the bidirectional relationship between metabolic syndrome and thyroid autoimmunity: a Mendelian randomization study.

Background: Observational studies have reported a possible association between metabolic syndrome (MetS) and thyroid autoimmunity. Nevertheless, the relationship between thyroid autoimmunity and MetS remains unclear. The objective of this research was to assess the causal impact of MetS on thyroid autoimmunity through the utilization of Mendelian randomization (MR) methodology. Methods: We performed bidirectional MR to elucidate the causal relationship between MetS and their components and thyroid autoimmunity (positivity of TPOAb). Single nucleotide polymorphisms (SNPs) of MetS and its components were obtained from the publicly available genetic variation summary database. The Thyroidomics Consortium conducted a genome-wide association analysis, which provided summary-level data pertaining to thyroid autoimmunity. The study included several statistical methods, including the inverse variance weighting method (IVW), weighted median, simple mode, weight mode, and MR-Egger methods, to assess the causal link. In addition, to ensure the stability of the results, a sensitivity analysis was conducted. Results: IVW showed that MetS reduced the risk of developing thyroid autoimmunity (OR = 0.717, 95% CI = 0.584 - 0.88, P = 1.48E-03). The investigation into the causative association between components of MetS and thyroid autoimmune revealed a statistically significant link between triglycerides levels and the presence of thyroid autoimmunity (IVW analysis, OR = 0.603, 95%CI = 0.45 -0.807, P = 6.82E-04). The reverse analysis did not reveal any causal relationship between thyroid autoimmunity and MetS, including its five components. Conclusions: We have presented new genetic evidence demonstrating that MetS and its triglyceride components may serve as potential protective factors against thyroid autoimmunity.

High-Power-Density Rechargeable Hybrid Alkali/Acid Zn-Air Battery Performance Through Value-Added Conversion Charging.

Rechargeable Zn-air batteries (ZABs) are considered highly competitive technologies for meeting the energy demands of the next generation, whether for energy storage or portable power. However, their practical application is hindered by critical challenges such as low voltage, CO2 poisoning at the cathode, low power density, and poor charging efficiency Herein, a rechargeable hybrid alkali/acid Zn-air battery (h-RZAB) that effectively separates the discharge process in an acidic environment from the charging process in an alkaline environment, utilizing oxygen reduction reaction (ORR) and glycerol oxidation reaction (GOR) respectively is reported. Compared to previously reported ZABs, this proof-of-concept device demonstrates impressive performance, exhibiting a high power density of 562.7 mW cm-2 and a high operating voltage during discharging. Moreover, the battery requires a significantly reduced charging voltage due to the concurrent utilization of biomass-derived glycerol, resulting in practical and cost-effective advantages. The decoupled system offers great flexibility for intermittently generated renewable power sources and presents cost advantages over traditional ZABs. As a result, this technology holds significant promise in opening avenues for the future development of renewable energy-compatible electrochemical devices.

Fixed-point algorithms for solving the critical value and upper tail quantile of Kuiper's statistics.

Kuiper's statistic is a good measure for the difference of ideal distribution and empirical distribution in the goodness-of-fit test. However, it is a challenging problem to solve the critical value and upper tail quantile, or simply Kuiper pair, of Kuiper's statistics due to the difficulties of solving the nonlinear equation and reasonable approximation of infinite series. In this work, the contributions lie in three perspectives: firstly, the second order approximation for the infinite series of the cumulative distribution of the critical value is used to achieve higher precision; secondly, the principles and fixed-point algorithms for solving the Kuiper pair are presented with details; finally, finally, a mistake about the critical value cnα for (α,n)=(0.01,30) in Kuiper's distribution table has been labeled and corrected where n is the sample capacity and α is the upper tail quantile. The algorithms are verified and validated by comparing with the table provided by Kuiper. The methods and algorithms proposed are enlightening and worth of introducing to the college students, computer programmers, engineers, experimental psychologists and so on.

Uncertainty of digital image correlation under video compression and DSP optimization.

The storage and transmission of videos at high spatial resolution remain a great challenge in image-based optical techniques. The uncertainty of digital image correlation (DIC) was assessed following speckle video compression under High Efficiency Video Coding (HEVC/H.265). First, the evaluation criterion for the DIC accuracy affected by compression was provided. The stability of H.265 video compression in DIC was studied considering different compressed frames under different target quantization parameters (QPs) and compression ratios (CRs). The deformation uncertainty of the DIC itself as affected by H.265 video compression was further investigated through uniform translation and non-uniform sinusoidal deformation performance. Moreover, the optimized digital speckle pattern (DSP) was re-evaluated considering video compression-induced uncertainty. DSPs with parameters of different diameters and randomness were compressed using various QPs and CRs. In addition, DSP evaluation was performed under both translation and non-homogeneous deformation conditions. The feasibility of the re-optimized DSP under H.265 video compression was validated using a defective bending beam, and DSP videos with a speckle size of 8 pixels reached a high CR within an acceptable margin of error.

LC-MS and MALDI-MSI-based metabolomic approaches provide insights into the spatial-temporal metabolite profiles of Tartary buckwheat achene development.

Tartary buckwheat, celebrated as the "king of grains" for its flavonoid and phenolic acid richness, has health-promoting properties. Despite significant morphological and metabolic variations in mature achenes, research on their developmental process is limited. Utilizing Liquid chromatography-mass spectrometry and atmospheric pressure matrix-assisted laser desorption/ionization mass spectrometry imaging, we conducted spatial-temporal metabolomics on two cultivars during achene development. Metabolic profiles including 17 phenolic acids and 83 flavonoids are influenced by both varietal distinctions and developmental intricacies. Notably, flavonols, as major flavonoids, accumulated with achene ripening and showed a tissue-specific distribution. Specifically, flavonol glycosides and aglycones concentrated in the embryo, while methylated flavonols and procyanidins in the hull. Black achenes at the green achene stage have higher bioactive compounds and enhanced antioxidant capacity. These findings provide insights into spatial and temporal characteristics of metabolites in Tartary buckwheat achenes and serve as a theoretical guide for selecting optimal resources for food production.

Sex-specific associations of plasma neutrophil gelatinase-associated lipocalin (NGAL) with cognition in patients with drug-naïve schizophrenia.

This present study aimed to investigate the sex-specific association of plasma neutrophil gelatinase-associated lipocalin (NGAL) with cognition in drug-naïve schizophrenia patients for the first time. A total of 204 participants in this study, including 137 drug-naïve schizophrenia (DNS) patients and 67 healthy controls (HCs). All participants completed the Measurements and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) Consensus Cognitive Battery (MCCB), and were collected fasting venous blood for NGAL measurement. DNS patients also complete the Positive and Negative Syndrome Scale (PANSS). Partial correlation analysis and multiple linear regression were used to explore sex-specific associations between NGAL and cognition. All dimensions of MCCB scores were significantly lower in both male and female DNS patients than HCs. Sex differences were significant in cognitive performance in both DNS patients and HCs. Female DNS patients experienced poorer working memory and reason& problem solving than male patients. Female HCs performed a better attention/vigilance and visual learning, a poorer reason& problem solving than male HCs. In patients with DNS, NGAL levels were negatively associated with positive subscale of PANSS and positively associated with working memory and visual learning only in female. However, there was no significant correlation between NGAL levels and all cognitive tests in both male and female HCs. Regression model showed that higher level of NGAL was an independent protective factor for cognitive performance in female patients with DNS, whereas there was no such role in male patients. Our findings suggest sex specificity between NGAL levels and cognitive performance in DNS patients.

A wideband, high-resolution vector spectrum analyzer for integrated photonics.

The analysis of optical spectra-emission or absorption-has been arguably the most powerful approach for discovering and understanding matter. The invention and development of many kinds of spectrometers have equipped us with versatile yet ultra-sensitive diagnostic tools for trace gas detection, isotope analysis, and resolving hyperfine structures of atoms and molecules. With proliferating data and information, urgent and demanding requirements have been placed today on spectrum analysis with ever-increasing spectral bandwidth and frequency resolution. These requirements are especially stringent for broadband laser sources that carry massive information and for dispersive devices used in information processing systems. In addition, spectrum analyzers are expected to probe the device's phase response where extra information is encoded. Here we demonstrate a novel vector spectrum analyzer (VSA) that is capable of characterizing passive devices and active laser sources in one setup. Such a dual-mode VSA can measure loss, phase response, and dispersion properties of passive devices. It also can coherently map a broadband laser spectrum into the RF domain. The VSA features a bandwidth of 55.1 THz (1260-1640 nm), a frequency resolution of 471 kHz, and a dynamic range of 56 dB. Meanwhile, our fiber-based VSA is compact and robust. It requires neither high-speed modulators and photodetectors nor any active feedback control. Finally, we employ our VSA for applications including characterization of integrated dispersive waveguides, mapping frequency comb spectra, and coherent light detection and ranging (LiDAR). Our VSA presents an innovative approach for device analysis and laser spectroscopy, and can play a critical role in future photonic systems and applications for sensing, communication, imaging, and quantum information processing.

Serum metabolism alteration behind different etiology, diagnosis, and prognosis of disorders of consciousness.

BACKGROUND: Patients with disorders of consciousness (DoC) exhibit varied revival outcomes based on different etiologies and diagnoses, the mechanisms of which remain largely unknown. The fluctuating clinical presentations in DoC pose challenges in accurately assessing consciousness levels and prognoses, often leading to misdiagnoses. There is an urgent need for a deeper understanding of the physiological changes in DoC and the development of objective diagnostic and prognostic biomarkers to improve treatment guidance. METHODS: To explore biomarkers and understand the biological processes, we conducted a comprehensive untargeted metabolomic analysis on serum samples from 48 patients with DoC. Patients were categorized based on etiology (TBI vs. non-TBI), CRS-R scores, and prognosis. Advanced analytical techniques, including PCA and OPLS-DA models, were employed to identify differential metabolites. RESULTS: Our analysis revealed a distinct separation in metabolomic profiles among the different groups. The primary differential metabolites distinguishing patients with varying etiologies were predominantly phospholipids, with a notable decrease in glycerophospholipids observed in the TBI group. Patients with higher CRS-R scores exhibited a pattern of impaired carbohydrate metabolism coupled with enhanced lipid metabolism. Notably, serum concentrations of both LysoPE and PE were reduced in patients with improved outcomes, suggesting their potential as prognostic biomarkers. CONCLUSIONS: Our study underscores the critical role of phospholipid metabolism in the brain's metabolic alterations in patients with DoC. It identifies key biomarkers for diagnosis and prognosis, offering insights that could lead to novel therapeutic targets. These findings highlight the value of metabolomic profiling in understanding and potentially treating DoC.

Unveiling the anticancer effects of SGLT-2i: mechanisms and therapeutic potential.

Cancer and diabetes are significant diseases that pose a threat to human health. Their interconnection is complex, particularly when they coexist, often necessitating multiple therapeutic approaches to attain remission. Sodium-glucose cotransporter protein two inhibitors (SGLT-2i) emerged as a treatment for hyperglycemia, but subsequently exhibited noteworthy extra-glycemic properties, such as being registered for the treatment of heart failure and chronic kidney disease, especially with co-existing albuminuria, prompting its assessment as a potential treatment for various non-metabolic diseases. Considering its overall tolerability and established use in diabetes management, SGLT-2i may be a promising candidate for cancer therapy and as a supplementary component to conventional treatments. This narrative review aimed to examine the potential roles and mechanisms of SGLT-2i in the management of diverse types of cancer. Future investigations should focus on elucidating the antitumor efficacy of individual SGLT-2i in different cancer types and exploring the underlying mechanisms. Additionally, clinical trials to evaluate the safety and feasibility of incorporating SGLT-2i into the treatment regimen of specific cancer patients and determining appropriate dosage combinations with established antitumor agents would be of significant interest.

Associations between corneal curvature and other anterior segment biometrics in young myopic adults.

To investigate the associations between corneal curvature (CC) and other anterior segment biometrics in young myopic adults. In this retrospective multi-center study, 7893 young myopic adults were included. CC and other anterior segment biometrics were measured by Scheimpflug imaging (Pentacam). CC was defined as SimK at central 3 mm area, and other anterior segment biometrics included white-to-white corneal diameter (WTW), central corneal thickness (CCT), corneal volume (CV) at 3 mm, 5 mm, and 7 mm area, anterior corneal astigmatism (ACA), posterior corneal astigmatism (PCA), anterior corneal eccentricity (ACE) and asphericity (ACAP), posterior corneal eccentricity (PCE) and asphericity (PCAP), anterior chamber depth (ACD), and anterior chamber volume (ACV). Univariate regression analyses were used to assess the associations between CC and other anterior segment biometrics, and multivariate regression analyses were further performed to adjusted for age, gender and spherical equivalent. CC was higher in patients of female gender and higher myopia (all P < 0.05). Eyes in higher CC quartiles had lower WTW, thinner CCT, lower CV at 3 mm and 5 mm, lower ACD, and lower ACV (all P < 0.001), but had larger ACA, larger PCA, less PCE and less PCAP (all P < 0.001), compared to eyes in lower CC quartiles. The trends of CV at 7 mm, ACE and ACAP were inconsistent in different CC quartiles. After adjusting for age, gender and spherical equivalent with multivariate linear regression, CC was positively correlated to CV at 7 mm (ßs = 0.069), ACA (ßs = 0.194), PCA (ßs = 0.187), ACE (ßs = 0.072), PCAP (ßs = 0.087), and ACD (ßs = 0.027) (all P < 0.05), but was negatively correlated to WTW (ßs = - 0.432), CCT (ßs = - 0.087), CV-3 mm (ßs = - 0.066), ACAP (ßs = - 0.043), PCE (ßs = - 0.062), and ACV (ßs = - 0.188) (all P < 0.05). CC was associated with most of the other anterior segment biometrics in young myopic adults. These associations are important for better understanding of the interactions between different anterior segment structures in young myopic patients, and are also useful for the exploration of the pathogenesis of myopia.

Regional analysis to delineate intrasample heterogeneity with RegionalST.

MOTIVATION: Spatial transcriptomics has greatly contributed to our understanding of spatial and intra-sample heterogeneity, which could be crucial for deciphering the molecular basis of human diseases. Intra-tumor heterogeneity, e.g. may be associated with cancer treatment responses. However, the lack of computational tools for exploiting cross-regional information and the limited spatial resolution of current technologies present major obstacles to elucidating tissue heterogeneity. RESULTS: To address these challenges, we introduce RegionalST, an efficient computational method that enables users to quantify cell type mixture and interactions, identify sub-regions of interest, and perform cross-region cell type-specific differential analysis for the first time. Our simulations and real data applications demonstrate that RegionalST is an efficient tool for visualizing and analyzing diverse spatial transcriptomics data, thereby enabling accurate and flexible exploration of tissue heterogeneity. Overall, RegionalST provides a one-stop destination for researchers seeking to delve deeper into the intricacies of spatial transcriptomics data. AVAILABILITY AND IMPLEMENTATION: The implementation of our method is available as an open-source R/Bioconductor package with a user-friendly manual available at https://bioconductor.org/packages/release/bioc/html/RegionalST.html.

Molecular characterization, expression and antibacterial function of a macin, HdMac, from Haliotis discus hannai.

Macins are a family of antimicrobial peptides, which play multiple roles in the elimination of invading pathogens. In the present study, a macin was cloned and characterized from Pacific abalone Haliotis discus hannai (Designated as HdMac). Analysis of the conserved domain suggested that HdMac was a new member of the macin family. In non-stimulated abalones, HdMac transcripts were constitutively expressed in all five tested tissues, especially in hemocytes. After Vibrio harveyi stimulation, the expression of HdMac mRNA in hemocytes was significantly up-regulated at 12 hr (P < 0.01). RNAi-mediated knockdown of HdMac transcripts affected the survival rates of abalone against V. harveyi. Moreover, recombinant protein of HdMac (rHdMac) exhibited high antibacterial activities against invading bacteria, especially for Vibrio anguillarum. In addition, rHdMac possessed binding activities towards glucan, lipopolysaccharides (LPS), and peptidoglycan (PGN), but not chitin in vitro. Membrane integrity analysis revealed that rHdMac could increase the membrane permeability of bacteria. Meanwhile, both the phagocytosis and chemotaxis ability of hemocytes could be significantly enhanced by rHdMac. Overall, the results showed that HdMac could function as a versatile molecule involved in immune responses of H. discus hannai.

Epidemiologic association and shared genetic architecture between cataract and hearing difficulties among middle-aged and older adults.

Age-related cataract and hearing difficulties are major sensory disorders that often co-exist in the global-wide elderly and have a tangible influence on the quality of life. However, the epidemiologic association between cataract and hearing difficulties remains unexplored, while little is known about whether the two share their genetic etiology. We first investigated the clinical association between cataract and hearing difficulties using the UK Biobank covering 502,543 individuals. Both unmatched analysis (adjusted for confounders) and a matched analysis (one control matched for each patient with cataract according to confounding factors) were undertaken and confirmed that cataract was associated with hearing difficulties (OR, 2.12; 95% CI, 1.98-2.27; OR, 2.03; 95% CI, 1.86-2.23, respectively). Furthermore, we explored and quantified the shared genetic architecture of these two complex sensory disorders at the common variant level using the bivariate causal mixture model (MiXeR) and conditional/conjunctional false discovery rate method based on the largest available genome-wide association studies of cataract (N = 585,243) and hearing difficulties (N = 323,978). Despite detecting only a negligible genetic correlation, we observe polygenic overlap between cataract and hearing difficulties and identify 6 shared loci with mixed directions of effects. Follow-up analysis of the shared loci implicates candidate genes QKI, STK17A, TYR, NSF, and TCF4 likely contribute to the pathophysiology of cataracts and hearing difficulties. In conclusion, this study demonstrates the presence of epidemiologic association between cataract and hearing difficulties and provides new insights into the shared genetic architecture of these two disorders at the common variant level.