Global marine microbial diversity and its potential in bioprospecting.

The past two decades has witnessed a remarkable increase in the number of microbial genomes retrieved from marine systems1,2. However, it has remained challenging to translate this marine genomic diversity into biotechnological and biomedical applications3,4. Here we recovered 43,191 bacterial and archaeal genomes from publicly available marine metagenomes, encompassing a wide range of diversity with 138 distinct phyla, redefining the upper limit of marine bacterial genome size and revealing complex trade-offs between the occurrence of CRISPR-Cas systems and antibiotic resistance genes. In silico bioprospecting of these marine genomes led to the discovery of a novel CRISPR-Cas9 system, ten antimicrobial peptides, and three enzymes that degrade polyethylene terephthalate. In vitro experiments confirmed their effectiveness and efficacy. This work provides evidence that global-scale sequencing initiatives advance our understanding of how microbial diversity has evolved in the oceans and is maintained, and demonstrates how such initiatives can be sustainably exploited to advance biotechnology and biomedicine.

Cell transcriptomic atlas of the non-human primate Macaca fascicularis.

Studying tissue composition and function in non-human primates (NHPs) is crucial to understand the nature of our own species. Here we present a large-scale cell transcriptomic atlas that encompasses over 1 million cells from 45 tissues of the adult NHP Macaca fascicularis. This dataset provides a vast annotated resource to study a species phylogenetically close to humans. To demonstrate the utility of the atlas, we have reconstructed the cell-cell interaction networks that drive Wnt signalling across the body, mapped the distribution of receptors and co-receptors for viruses causing human infectious diseases, and intersected our data with human genetic disease orthologues to establish potential clinical associations. Our M. fascicularis cell atlas constitutes an essential reference for future studies in humans and NHPs.

CropGS-Hub: a comprehensive database of genotype and phenotype resources for genomic prediction in major crops.

The explosive amount of multi-omics data has brought a paradigm shift both in academic research and further application in life science. However, managing and reusing the growing resources of genomic and phenotype data points presents considerable challenges for the research community. There is an urgent need for an integrated database that combines genome-wide association studies (GWAS) with genomic selection (GS). Here, we present CropGS-Hub, a comprehensive database comprising genotype, phenotype, and GWAS signals, as well as a one-stop platform with built-in algorithms for genomic prediction and crossing design. This database encompasses a comprehensive collection of over 224 billion genotype data and 434 thousand phenotype data generated from >30 000 individuals in 14 representative populations belonging to 7 major crop species. Moreover, the platform implemented three complete functional genomic selection related modules including phenotype prediction, user model training and crossing design, as well as a fast SNP genotyper plugin-in called SNPGT specifically built for CropGS-Hub, aiming to assist crop scientists and breeders without necessitating coding skills. CropGS-Hub can be accessed at https://iagr.genomics.cn/CropGS/.

STOmicsDB: a comprehensive database for spatial transcriptomics data sharing, analysis and visualization.

Recent technological developments in spatial transcriptomics allow researchers to measure gene expression of cells and their spatial locations at the single-cell level, generating detailed biological insight into biological processes. A comprehensive database could facilitate the sharing of spatial transcriptomic data and streamline the data acquisition process for researchers. Here, we present the Spatial TranscriptOmics DataBase (STOmicsDB), a database that serves as a one-stop hub for spatial transcriptomics. STOmicsDB integrates 218 manually curated datasets representing 17 species. We annotated cell types, identified spatial regions and genes, and performed cell-cell interaction analysis for these datasets. STOmicsDB features a user-friendly interface for the rapid visualization of millions of cells. To further facilitate the reusability and interoperability of spatial transcriptomic data, we developed standards for spatial transcriptomic data archiving and constructed a spatial transcriptomic data archiving system. Additionally, we offer a distinctive capability of customizing dedicated sub-databases in STOmicsDB for researchers, assisting them in visualizing their spatial transcriptomic analyses. We believe that STOmicsDB could contribute to research insights in the spatial transcriptomics field, including data archiving, sharing, visualization and analysis. STOmicsDB is freely accessible at https://db.cngb.org/stomics/.

A high-resolution haplotype-resolved Reference panel constructed from the China Kadoorie Biobank Study.

Precision medicine depends on high-accuracy individual-level genotype data. However, the whole-genome sequencing (WGS) is still not suitable for gigantic studies due to budget constraints. It is particularly important to construct highly accurate haplotype reference panel for genotype imputation. In this study, we used 10 000 samples with medium-depth WGS to construct a reference panel that we named the CKB reference panel. By imputing microarray datasets, it showed that the CKB panel outperformed compared panels in terms of both the number of well-imputed variants and imputation accuracy. In addition, we have completed the imputation of 100 706 microarrays with the CKB panel, and the after-imputed data is the hitherto largest whole genome data of the Chinese population. Furthermore, in the GWAS analysis of real phenotype height, the number of tested SNPs tripled and the number of significant SNPs doubled after imputation. Finally, we developed an online server for offering free genotype imputation service based on the CKB reference panel (https://db.cngb.org/imputation/). We believe that the CKB panel is of great value for imputing microarray or low-coverage genotype data of Chinese population, and potentially mixed populations. The imputation-completed 100 706 microarray data are enormous and precious resources of population genetic studies for complex traits and diseases.

Standards recommendations for the Earth BioGenome Project.

A global international initiative, such as the Earth BioGenome Project (EBP), requires both agreement and coordination on standards to ensure that the collective effort generates rapid progress toward its goals. To this end, the EBP initiated five technical standards committees comprising volunteer members from the global genomics scientific community: Sample Collection and Processing, Sequencing and Assembly, Annotation, Analysis, and IT and Informatics. The current versions of the resulting standards documents are available on the EBP website, with the recognition that opportunities, technologies, and challenges may improve or change in the future, requiring flexibility for the EBP to meet its goals. Here, we describe some highlights from the proposed standards, and areas where additional challenges will need to be met.

Microfluidic Immunosensing Platform Based on a Rolling Circle Amplification-Assisted DNA Dendrimer Probe for Portable and Sensitive Detection of Allergen-Specific IgE.

The robust point-of-care platform for sensitive, multiplexed, and affordable detection of allergen-specific IgE (sIgE) is an urgent demand in component-resolved diagnostics. Here, we developed a microfluidic immunosensing platform based on a rolling circle amplification-assisted DNA dendrimer probe for sensitive detection of multiple sIgEs. The versatile multichannel microfluidic whole blood analytical device integrates cell filtration, recombinant antigen-modified magnetic enrichment, and DNA dendrimer probe-amplified signal transduction for portable on-chip analysis. Three sIgEs against common oyster allergens were simultaneously detected in blood samples by simple smartphone-based imaging without any pretreatment. The quantitative detection of multiple allergen-specific antibodies on the platform was achieved with limits of detection of less than 50 pg/mL, exhibiting superior sensitivity compared to most point-of-care testing. The detection results of 55 serum samples and 4 whole blood samples were 100% consistent with the ELISA results, confirming the accuracy and stability of our platform. Additionally, the reversible combination of hexahistidine6-tag and Ni-IMAC magbead was elegantly utilized on the immunosensing platform for desired reversibility. With the advantages of general applicability, high sensitivity, and reversibility, the DNA dendrimer-based microfluidic immunosensing platform provides great potential for the portable detection of immune proteins as a point-of-care platform in disease diagnostics and biological analysis.

Precise diagnosis of a hereditary spherocytosis patient with complicated hematological phenotype.

Hereditary spherocytosis (HS) is one of the most common causes of hereditary hemolytic anemia. The current diagnostic guidelines for HS are mainly based on a combination of physical examination and laboratory investigation. However, some patients present with complicated clinical manifestations that cannot be explained by routine diagnostic protocols. Here, we report a rare HS case of mild anemia with extremely high indirect bilirubin levels and high expression of fetal hemoglobin. Using whole exome sequencing analysis, this patient was identified as a heterozygous carrier of a de novo SPTB nonsense mutation (c.605G > A; p.W202*) and a compound heterozygous carrier of known UGT1A1 and KLF1 mutations. This genetic analysis based on the interpretation of the patient's genomic data not only achieved precise diagnosis by an excellent explanation of the complicated phenotype but also provided valuable suggestions for subsequent appropriate approaches for treatment, surveillance and prophylaxis.

Attitude and heading measurement based on adaptive complementary Kalman filter for PS/MIMU integrated system.

The bionic polarization sensor (PS)/MEMS inertial measurement unit (MIMU) integrated system can provide reliable attitude and heading information for unmanned vehicles in the case of GNSS rejection. However, the existing measurement methods have poor adaptability to inclining, sheltering, and other harsh environments, and do not make full use of the complementary characteristics of the gyroscopes, accelerometers, and PS, which seriously affects the system performance. Therefore, this paper proposes an attitude and heading measurement method based on an adaptive complementary Kalman filter (ACKF), which corrects the gyroscopes according to the gravity measured by the accelerometers to improve the attitude accuracy and fuses the IMU heading and tilt-compensated polarization heading by Kalman optimal estimation. On this basis, the maximum correlation entropy of the measured gravity and the theoretical gravity is used to construct an adaptive factor to realize the adaptive complementary of the gyroscopes and the accelerometers. Finally, the effectiveness of the method is verified by the outdoor rotation test without occlusion and the vehicle test with occlusion. Compared with the traditional Kalman filter, the pitch, roll, and heading RMSE of the vehicle test are reduced by 89.3%, 93.2% and, 9.6% respectively, which verifies the great advantages.

SNPscan Combined With CNVplex as a High-Performance Diagnostic Method for Thalassemia.

OBJECTIVE: Thalassemia is a Mendelian-inherited blood disorder with severe consequences, including disability and mortality, making it a significant public health concern. Therefore, there is an urgent need for precise diagnostic technologies. We introduce two innovative diagnostic techniques for thalassemia, SNPscan and CNVplex, designed to enhance molecular diagnostics of thalassemia. METHODS: The SNPscan and CNVplex assays utilize variations in PCR product length and fluorescence to identify multiple mutations. In the SNPscan method, we designed three probes per locus: two 5' and one 3', and incorporated allele identification link sequences into one of the 5' probes to distinguish the alleles. The detection system was designed for 67 previously reported loci in the Chinese population for a specific genetic condition. CNVplex identifies deletion types by analyzing the specific positions of probes within the globin gene. This innovative approach enables the detection of six distinct deletional mutations, enhancing the precision of thalassemia diagnostics. We evaluated and refined the methodologies in a training cohort of 100 individuals with confirmed HBA and HBB genotypes. The validation cohort, consisting of 1647 thalassemia patients and 100 healthy controls, underwent a double-blind study. Traditional diagnostic techniques served as the control methods. RESULTS: In the training set of 100 samples, 10 mutations (Hb QS, Hb CS, Hb Westmead, CD17, CD26, CD41-42, IVS-II-654, --SEA, -α3.7 and -α4.2) were identified, consistent with those identified by traditional methods. The validation study showed that SNPscan/CNVplex offered superior molecular diagnostic capabilities for thalassemia, with 100% accuracy compared to 99.43% for traditional methods. Notably, the assay identified three previously undetected mutations in 10 cases, including two deletion mutations (Chinese Gγ(Aγδß)0 del and SEA-HPFH), and one non-deletion mutation (Hb Q-Thailand). CONCLUSIONS: The SNPscan/CNVplex assay is a cost-effective and user-friendly tool for diagnosing thalassemia, demonstrating high accuracy and reliability, and showing great potential as a primary diagnostic method in clinical practice.

A novel gain-of-function PIP4K2A mutation elevates the expression of ß-globin and aggravates the severity of α-thalassemia.

Haemoglobin H (Hb H) disease (intermediate status of α-thalassemia) shows marked phenotypic variability from asymptomatic to severe anaemia. Apart from the combined ß-thalassemia allele ameliorating clinical severity, reports of genetic modifier genes affecting the phenotype of Hb H disease are scarce which bring inconvenience to precise diagnosis and genetic counselling of the patients. Here, we present a novel mutation (c.948C>A, p.S316R) in the PIP4K2A gene in a female Hb H disease patient who displayed moderate anaemia and a relatively high Hb H level. Haematological analysis in her family members revealed that individuals carrying this mutation have upregulated ß-globin expression, leading to a more imbalanced ß/α-globin ratio and more Hb H inclusion bodies in peripheral red blood cells. According to functional experiments, the mutant PIP4K2A protein exhibits enhanced protein stability, increased kinase activity and a stronger regulatory effect on downstream proteins, suggesting a gain-of-function mutation. Moreover, introduction of the S316R mutation into HUDEP-2 cells increased expression of ß-globin, further inhibiting erythroid differentiation and terminal enucleation. Thus, the S316R mutation is a novel genetic factor associated with ß-globin expression, and the PIP4K2A gene is a new potential modifier gene affecting the α-thalassemia phenotype.

Light-Driven Photocatalytic-Photothermal Synergetic System for Portable and Sensitive Nucleic Acid Quantification.

Photosensitizers and photothermal agents have attracted increasing attention for in vitro diagnosis, but the combination remains challenging. Herein, a light-driven photocatalytic-photothermal synergetic system integrated microfluidic distance-based analytical device (PCPT-µDAD) for visual, portable, sensitive, and quantitative detection of targets was developed. Target DNA was recognized and initiated the hybridization chain reaction to form a double-stranded DNA/SYBR Green I (dsDNA/SG-I) complex. By applying the photosensitization of the dsDNA/SG-I complex and the photothermal effect of oxidized 3,3',5,5'-tetramethylbenzidine, the target concentration can effectively translate into a visual distance signal readout. Importantly, the light-driven PCPT-µDAD greatly improves the controllability of catalytic reactions and signal amplification efficiency. The light-driven PCPT-µDAD shows a low limit of detection (fM level), good stability, and high reproducibility for nucleic acid detection.

Investigation of the mechanism of copy number variations involving the α-globin gene cluster on chromosome 16: two case reports and literature review.

Thalassemia is one of the most common single-gene disorder worldwide. An important genetic cause of thalassemia is copy number variations (CNVs) in the α-globin gene cluster. However, there is no unified summary and discussion on the detailed information and mechanisms of these CNVs. In this study, two novel CNVs, a tandem duplication (αααα159) and deletion (--259), were identified in two Chinese families with thalassemia patients, according to the results of hematologic analysis, routine genetic testing for thalassemia, multiplex ligation-dependent probe amplification (MLPA), next-generation sequencing (NGS) and other molecular methods. Co-inherited with ßCD41-42 mutation and --SEA deletion separately, αααα159 and --259 resulted in a patient with ß-thalassemia intermedia and a lethal fetus with Hb Bart's hydrops fetalis syndrome, respectively. Next, a literature review was performed to summarize all known CNVs involving the α-globin gene cluster. The molecular structure characteristics of these CNVs were analyzed and the possible mechanism was explored. It is the first time to analyze the generation mechanism of genome arrangements in the α-globin gene cluster systematically.

Stress response and tolerance mechanisms of NaHCO3 exposure based on biochemical assays and multi-omics approach in the liver of crucian carp (Carassius auratus).

The development and utilization of saline-alkaline water, an important backup resource, has received widespread attention. However, the underuse of saline-alkaline water, threatened by the single species of saline-alkaline aquaculture, seriously affects the development of the fishery economy. In this work, a 30-day NaHCO3 stress experimental study combined with analyses of untargeted metabolomics, transcriptome, and biochemical approaches was conducted on crucian carp to provide a better understanding of the saline-alkaline stress response mechanism in freshwater fish. This work revealed the relationships among the biochemical parameters, endogenous differentially expressed metabolites (DEMs), and differentially expressed genes (DEGs) in the crucian carp livers. The biochemical analysis showed that NaHCO3 exposure changed the levels of several physiological parameters associated with the liver, including antioxidant enzymes (SOD, CAT, GSH-Px), MDA, AKP, and CPS. According to the metabolomics study, 90 DEMs are involved in various metabolic pathways such as ketone synthesis and degradation metabolism, glycerophospholipid metabolism, arachidonic acid metabolism, and linoleic acid metabolism. In addition, transcriptomics data analysis showed that a total of 301 DEGs were screened between the control group and the high NaHCO3 concentration group, of which 129 up-regulated genes and 172 down-regulated genes. Overall, NaHCO3 exposure could cause lipid metabolism disorders and induce energy metabolism imbalance in the crucian carp liver. Simultaneously, crucian carp might regulate its saline-alkaline resistance mechanism by enhancing the synthesis of glycerophospholipid metabolism, ketone bodies, and degradation metabolism, at the same time increasing the vitality of antioxidant enzymes (SOD, CAT, GSH-Px) and nonspecific immune enzyme (AKP). Herein, all results will provide new insights into the molecular mechanisms underlying the stress responses and tolerance to saline-alkaline exposure in crucian carp.

The Inhibitory Effect of Magnolol on the Human TWIK1 Channel Is Related to G229 and T225 Sites.

TWIK1 (K2P1.1/KCNK1) belongs to the potassium channels of the two-pore domain. Its current is very small and difficult to measure. In this work, we used a 100 mM NH4+ extracellular solution to increase TWIK1 current in its stable cell line expressed in HEK293. Then, the inhibition of magnolol on TWIK1 was observed via a whole-cell patch clamp experiment, and it was found that magnolol had a significant inhibitory effect on TWIK1 (IC50 = 6.21 ± 0.13 µM). By molecular docking and alanine scanning mutagenesis, the IC50 of TWIK1 mutants G229A, T225A, I140A, L223A, and S224A was 20.77 ± 3.20, 21.81 ± 7.93, 10.22 ± 1.07, 9.55 ± 1.62, and 7.43 ± 3.20 µM, respectively. Thus, we conclude that the inhibition of the TWIK1 channel by magnolol is related to G229 and T225 on the P2- pore helix.

The Strength of hERG Inhibition by Erythromycin at Different Temperatures Might Be Due to Its Interacting Features with the Channels.

Erythromycin is one of the few compounds that remarkably increase ether-a-go-go-related gene (hERG) inhibition from room temperature (RT) to physiological temperature (PT). Understanding how erythromycin inhibits the hERG could help us to decide which compounds are needed for further studies. The whole-cell patch clamp technique was used to investigate the effects of erythromycin on hERG channels at different temperatures. While erythromycin caused a concentration-dependent inhibition of cardiac hERG channels, it also shifted the steady-state activation and steady-state inactivation of the channel to the left and significantly accelerated the onset of inactivation at both temperatures, although temperature itself caused a profound change in the dynamics of hERG channels. Our data also suggest that the binding pattern to S6 of the channels changes at PT. In contrast, cisapride, a well-known hERG blocker whose inhibition is not affected by temperature, does not change its critical binding sites after the temperature is raised to PT. Our data suggest that erythromycin is unique and that the shift in hERG inhibition may not apply to other compounds.

Projective Synchronization of Delayed Uncertain Coupled Memristive Neural Networks and Their Application.

In this article, the authors analyzed the nonlinear effects of projective synchronization between coupled memristive neural networks (MNNs) and their applications. Since the complete signal transmission is difficult under parameter mismatch and different projective factors, the delays, which are time-varying, and uncertainties have been taken to realize the projective synchronization of MNNs with multi-links under the nonlinear control method. Through the extended comparison principle and a new approach to dealing with the mismatched parameters, sufficient criteria have been determined under different types of projective factors and the framework of the Lyapunov-Krasovskii functional (LKF) for projective convergence of the coupled MNNs. Instead of the classical treatment for secure communication, the concept of error of synchronization between the drive and response systems has been applied to solve the signal encryption/decryption problem. Finally, the simulations in numerical form have been demonstrated graphically to confirm the adaptability of the theoretical results.

Biological modification of pentosans in wheat B starch wastewater and preparation of a composite film.

BACKGROUND: Petrochemical resources are becoming increasingly scarce, and petroleum-based plastic materials adversely impact the environment. Thus, replacement of petroleum-based materials with new and effective renewable materials is urgently required. RESULTS: In this study, a wheat pentosan-degrading bacterium (MXT-1) was isolated from wheat-processing plant wastewater. The MXT-1 strain was identified using molecular biology techniques. The degradation characteristics of the bacteria in wheat pentosan were analyzed. The results show that wheat pentosan was effectively degraded by bacteria. The molecular weight of fermented wheat pentosan decreased from 1730 to 257 kDa. The pentosan before and after the biological modification was mixed with chitosan to prepare a composite film. After fermentation, the water-vapor permeability of the wheat pentosan film decreased from 0.2769 to 0.1286 g mm (m2 h KPa)-1. Results obtained from the Fourier-transformed infrared experiments demonstrate that the wave number of the hydroxyl-stretching vibration peak of the membrane material decreased, and the width of the peak widened. The diffraction peak of the film shifted to the higher 2θ, as seen using X-ray diffraction. The cross-section of the modified composite membrane was observed via scanning electron microscopy, which revealed that the structure was denser; however, no detectable phase separation was observed. These results may indicate improved molecular compatibility between wheat pentosan and chitosan and stronger hydrogen bonding between the molecules. Given the increased number of short-chain wheat pentosan molecules, although the tensile strength of the film decreased, its flexibility increased after fermentation modification. CONCLUSION: The findings of this study established that the physical properties of polysaccharide films can be improved using strain MXT-1 to ferment and modify wheat pentosan. The compatibility and synergy between pentosan and chitosan molecules was substantially enhanced, and hydrogen bonding was strengthened after biological modification. Therefore, modified pentosan film could be a potential candidate material for edible packaging films.

Use of fulvic acid-like compounds from pulp-derived black liquor for enhancing the selenium content of peanut buds.

BACKGROUND: Cleaner production involving the extraction of useful material from the black liquor by-product of straw pulp would be environmentally beneficial and would permit increased wastewater usage. RESULTS: The fulvic-acid-like components of pulp black liquor (PFA) with molecular weights below 10 kDa were isolated. The chemical and physiological characteristics of PFAs were investigated. Selenite can enhance the selenium nutrition level of crops, but excessive selenite may be toxic to plant growth. In order to explore how to increase selenite tolerance and selenium accumulation in peanut, the effects of PFA on selenium-associated properties in peanut seedlings were examined by growing seedlings with sodium selenite (0, 5, 15, and 25 mg·L- 1 Na2SeO3, 15 mg·L- 1 Na2SeO3 solution containing 60 mg-C/L PFA, and 25 mg·L- 1 Na2SeO3 containing 60 mg-C/L PFA). CONCLUSION: The results showed that with 15 mg·L- 1 Na2SeO3, PFA significantly increased both the total and hypocotyl fresh weight of the seedlings but reduced the fresh weight of the root. PFA also effectively promoted the conversion of Se from inorganic to organic compounds in the root and hypocotyl, increased the soluble total sugar and soluble protein contents of the hypocotyl, and thus improved the edible quality and food safety of the selenium-enriched peanut buds. The results suggest that PFA can be used as an innovative bio-based substance for selenium-enriched sprout vegetable production.

Mitotically heritable epigenetic modifications of CmMYB6 control anthocyanin biosynthesis in chrysanthemum.

Flower color, which is determined by various chemical pigments, is a vital trait for ornamental plants, in which anthocyanin is a major component. However, the epigenetic regulation of anthocyanin biosynthesis remains poorly understood. During chrysanthemum cultivation, we found a heterochromatic chrysanthemum accession (YP) whose progeny generated by asexual reproduction contained both yellow-flowered (YP-Y) and pink-flowered (YP-P) plants. In this study, we aimed to elucidate the epigenetic mechanisms of different flower colors in the YP plant progeny. Metabolome and transcriptome analyses revealed that the difference in flower color between YP-Y and YP-P was caused by expression variation of the anthocyanin biosynthesis gene CmMYB6. Bisulfite sequencing revealed that methylation at the CmMYB6 promoter, especially in the CHH context, was higher in YP-Y than YP-P. After demethylation of the CmMYB6 promoter using the dCas9-TET1cd system, the flower color returned from yellow to pink. Furthermore, the methylation status of the CmMYB6 promoter was higher in YP-Y over three consecutive generations, indicating that this methylation status was heritable mitotically. Finally, investigation of other chrysanthemum cultivars showed that the methylation of CmMYB6 decreased gradually with the increase in anthocyanin content. These results lay an epigenetic foundation for the improvement of flower color in horticultural plants.