Programming and inheritance of parental DNA methylomes in mammals.

The reprogramming of parental methylomes is essential for embryonic development. In mammals, paternal 5-methylcytosines (5mCs) have been proposed to be actively converted to oxidized bases. These paternal oxidized bases and maternal 5mCs are believed to be passively diluted by cell divisions. By generating single-base resolution, allele-specific DNA methylomes from mouse gametes, early embryos, and primordial germ cell (PGC), as well as single-base-resolution maps of oxidized cytosine bases for early embryos, we report the existence of 5hmC and 5fC in both maternal and paternal genomes and find that 5mC or its oxidized derivatives, at the majority of demethylated CpGs, are converted to unmodified cytosines independent of passive dilution from gametes to four-cell embryos. Therefore, we conclude that paternal methylome and at least a significant proportion of maternal methylome go through active demethylation during embryonic development. Additionally, all the known imprinting control regions (ICRs) were classified into germ-line or somatic ICRs.

Sperm, but not oocyte, DNA methylome is inherited by zebrafish early embryos.

5-methylcytosine is a major epigenetic modification that is sometimes called "the fifth nucleotide." However, our knowledge of how offspring inherit the DNA methylome from parents is limited. We generated nine single-base resolution DNA methylomes, including zebrafish gametes and early embryos. The oocyte methylome is significantly hypomethylated compared to sperm. Strikingly, the paternal DNA methylation pattern is maintained throughout early embryogenesis. The maternal DNA methylation pattern is maintained until the 16-cell stage. Then, the oocyte methylome is gradually discarded through cell division and is progressively reprogrammed to a pattern similar to that of the sperm methylome. The passive demethylation rate and the de novo methylation rate are similar in the maternal DNA. By the midblastula stage, the embryo's methylome is virtually identical to the sperm methylome. Moreover, inheritance of the sperm methylome facilitates the epigenetic regulation of embryogenesis. Therefore, besides DNA sequences, sperm DNA methylome is also inherited in zebrafish early embryos.

Tet-mediated DNA methylation dynamics affect chromosome organization.

DNA Methylation is a significant epigenetic modification that can modulate chromosome states, but its role in orchestrating chromosome organization has not been well elucidated. Here we systematically assessed the effects of DNA Methylation on chromosome organization with a multi-omics strategy to capture DNA Methylation and high-order chromosome interaction simultaneously on mouse embryonic stem cells with DNA methylation dioxygenase Tet triple knock-out (Tet-TKO). Globally, upon Tet-TKO, we observed weakened compartmentalization, corresponding to decreased methylation differences between CpG island (CGI) rich and poor domains. Tet-TKO could also induce hypermethylation for the CTCF binding peaks in TAD boundaries and chromatin loop anchors. Accordingly, CTCF peak generally weakened upon Tet-TKO, which results in weakened TAD structure and depletion of long-range chromatin loops. Genes that lost enhancer-promoter looping upon Tet-TKO showed DNA hypermethylation in their gene bodies, which may compensate for the disruption of gene expression. We also observed distinct effects of Tet1 and Tet2 on chromatin organization and increased DNA methylation correlation on spatially interacted fragments upon Tet inactivation. Our work showed the broad effects of Tet inactivation and DNA methylation dynamics on chromosome organization.

An entropy-based approach for assessing the directional persistence of cell migration.

Cell migration, which is primarily characterized by directional persistence, is essential for the development of normal tissues and organs, as well as for numerous pathological processes. However, there is a lack of simple and efficient tools to analyze the systematic properties of persistence based on cellular trajectory data. Here, we present a novel approach, the entropy of angular distribution , which combines cellular turning dynamics and Shannon entropy to explore the statistical and time-varying properties of persistence that strongly correlate with cellular migration modes. Our results reveal the changes in the persistence of multiple cell lines that are tightly regulated by both intra- and extracellular cues, including Arpin protein, collagen gel/substrate, and physical constraints. Significantly, some previously unreported distinctive details of persistence have also been captured, helping to elucidate how directional persistence is distributed and evolves in different cell populations. The analysis suggests that the entropy of angular distribution-based approach provides a powerful metric for evaluating directional persistence and enables us to better understand the relationships between cellular behaviors and multiscale cues, which also provides some insights into the migration dynamics of cell populations, such as collective cell invasion.

Anodic Reconstructed p+-GaAs/a-InAsN for Stable and Efficient Photoelectrochemical Hydrogen Evolution.

The extremely poor solution stability and massive carrier recombination have seriously prevented III-V semiconductor nanomaterials from efficient and stable hydrogen production. In this work, an anodic reconstruction strategy based on group III-V active semiconductors is proposed for the first time, resulting in 19-times photo-gain. What matters most is that the device after anodic reconstruction shows very superior stability under the protracted photoelectrochemical (PEC) test over 8100 s, while the final photocurrent density does not decrease but rather increases by 63.15%. Using the experiment and DFT theoretical calculation, the anodic reconstruction mechanism is elucidated: through the oxidation of indium clusters and the migration of arsenic atoms, the reconstruction formed p+-GaAs/a-InAsN. The hole concentration of the former is increased by 10 times (5.64 × 1018 cm-1 increases up to 5.95 × 1019 cm-1) and the band gap of the latter one is reduced to a semi-metallic state, greatly strengthening the driving force of PEC water splitting. This work turns waste into treasure, transferring the solution instability into better efficiency.

SiC@NiO Core-Shell Nanowire Networks-Based Optoelectronic Synapses for Neuromorphic Computing and Visual Systems at High Temperature.

1D nanowire networks, sharing similarities of structure, information transfer, and computation with biological neural networks, have emerged as a promising platform for neuromorphic systems. Based on brain-like structures of 1D nanowire networks, neuromorphic synaptic devices can overcome the von Neumann bottleneck, achieving intelligent high-efficient sensing and computing function with high information processing rates and low power consumption. Here, high-temperature neuromorphic synaptic devices based on SiC@NiO core-shell nanowire networks optoelectronic memristors (NNOMs) are developed. Experimental results demonstrate that NNOMs attain synaptic short/long-term plasticity and modulation plasticity under both electrical and optical stimulation, and exhibit advanced functions such as short/long-term memory and "learning-forgetting-relearning" under optical stimulation at both room temperature and 200 °C. Based on the advanced functions under light stimulus, the constructed 5 × 3 optoelectronic synaptic array devices exhibit a stable visual memory function up to 200 °C, which can be utilized to develop artificial visual systems. Additionally, when exposed to multiple electronic or optical stimuli, the NNOMs effectively replicate the principles of Pavlovian classical conditioning, achieving visual heterologous synaptic functionality and refining neural networks. Overall, with abundant synaptic characteristics and high-temperature thermal stability, these neuromorphic synaptic devices offer a promising route for advancing neuromorphic computing and visual systems.

SnapHiC: a computational pipeline to identify chromatin loops from single-cell Hi-C data.

Single-cell Hi-C (scHi-C) analysis has been increasingly used to map chromatin architecture in diverse tissue contexts, but computational tools to define chromatin loops at high resolution from scHi-C data are still lacking. Here, we describe Single-Nucleus Analysis Pipeline for Hi-C (SnapHiC), a method that can identify chromatin loops at high resolution and accuracy from scHi-C data. Using scHi-C data from 742 mouse embryonic stem cells, we benchmark SnapHiC against a number of computational tools developed for mapping chromatin loops and interactions from bulk Hi-C. We further demonstrate its use by analyzing single-nucleus methyl-3C-seq data from 2,869 human prefrontal cortical cells, which uncovers cell type-specific chromatin loops and predicts putative target genes for noncoding sequence variants associated with neuropsychiatric disorders. Our results indicate that SnapHiC could facilitate the analysis of cell type-specific chromatin architecture and gene regulatory programs in complex tissues.

Polarization-independent edge detection based on the spin-orbit interaction of light.

In previous edge detection schemes based on the spin-orbit interaction of light, the direction and intensity of the edge-enhanced images are influenced by the incident polarization state. In this study, we develop an edge detection strategy that is insensitive to changes in both the incident polarization and the incident angle. The output intensity and transfer function remain entirely impervious to changes in incident polarization, being explicitly formulated as functions of the incident angle, specifically in terms of cot 2⁡θ i and cot⁡θ i , respectively. This behavior is attributed to the opposing nature of the polarization components E~r H-H and E~r V-V in the x-direction after undergoing mapping through the Glan polarizer, while the sum of polarization components E~r H-V and E~r V-H in the y-direction can be simplified to terms independent of incident polarization. Furthermore, we propose a metasurface design to achieve the required optical properties in order to realize the derived edge detection scheme.

Neural-network-based carrier-less amplitude phase modulated signal generation and end-to-end optimization for fiber-terahertz integrated communication system.

In fiber-terahertz integrated communication systems, nonlinear distortion and inter-symbol interference (ISI) will degrade transmission performance. Pre-compensation is an efficient method to handle the channel distortion as it can avoid noise boosting during channel compensation and reduce receiver side signal processing algorithmic complexity at user-end (UE) considering the asymmetric access scenario. In this paper, we propose and experimentally demonstrate a neural-network (NN)-based carrier-less amplitude phase (CAP) modulated signal generation and end-to-end optimization method for a fiber-terahertz integrated communication system. The CAP signal is generated directly from quadrature amplitude modulation symbols and pre-compensated through a transmitter NN, which allows the receiver to demodulate the signal with simple linear digital signal process (DSP). In generating the CAP signal, the NN based transmitter learns a group of filters, which can generate, up-convert, and pre-compensate the signals. Based on the proposed method, a fiber-terahertz integration access system at 220 GHz is demonstrated and a sensitivity gain of 1.2 dB is achieved at a transmission speed of 50 Gbps and the forward error correction (FEC) bit error rate (BER) threshold of 1 × 10-2 compared with the baseline after 10-km fiber transmission and 1-m wireless delivering.

Net-432-Gb/s/λ PS-PAM transmission based on advanced DSP and single DAC for 400†G/λ IM/DD links.

The escalating surge in datacenter traffic creates a pressing demand for augmenting the capacity of cost-effective intensity modulation and direct detection (IM/DD) systems. In this Letter, we report the demonstration of the single-lane 128-GBaud probabilistically shaped (PS)-PAM-20 IM/DD transmission using only a single digital-to-analog converter (DAC) for a net 400 G/λ system. Based on the advanced digital signal processing (DSP), we achieve net bitrates of up to 437 Gb/s for optical back-to-back and 432 Gb/s after the 0.5-km SSMF transmission in the C-band with 128-Gbaud PS-PAM-20 signals. This work is the latest demonstration on ultra-high-order PS-PAM signals achieving net bitrates exceeding 400 Gb/s despite symbol rate limitations. Notably, to the best of our knowledge, the realized net information rate ([net bitrate]/[symbol rate]) of 3.37 marks a new achievement within the domain of 400 G/λ IM/DD systems, with promising implications for enhancing bandwidth efficiency in the upcoming 1.6-Tb Ethernet scenario.

Janus Flexible Device with Microcone Channels for Sampling and Analysis of Biological Microfluidics.

Controlling the spontaneous directional transport of droplets plays an important role in the application of microchemical reactions and microdroplet detection. Although the relevant technologies have been widely studied, the existing spontaneous droplet transport strategies still face problems of complex structure, single function, and poor flexibility. Inspired by the spontaneous droplet transport strategy in nature, an asymmetric wettability surface with microcone channels (AWS-MC) is prepared on a flexible fabric by combining surface modification and femtosecond laser manufacturing technology. On this surface, the capillary force and Laplace pressure induced by the wettability gradient and the geometric structure gradient drive the droplet transport from the hydrophobic surface to the hydrophilic surface. Notably, droplets in adjacent hydrophilic regions do not exchange substances even if the gap in the hydrophilic region is only 1 mm, which provides an ideal platform for numerous detections by a single drop. The droplet transport strategy does not require external energy and can adapt to the manipulation of various droplet types. Application of this surface in the blood of organisms is demonstrated. This work provides an effective method for microdroplet-directed self-transport and microdroplet detection.

Sediment DNA Records the Critical Transition of Bacterial Communities in the Arid Lake.

It is necessary to predict the critical transition of lake ecosystems due to their abrupt, non-linear effects on social-economic systems. Given the promising application of paleolimnological archives to tracking the historical changes of lake ecosystems, it is speculated that they can also record the lake's critical transition. We studied Lake Dali-Nor in the arid region of Inner Mongolia because of the profound shrinking the lake experienced between the 1300 s and the 1600 s. We reconstructed the succession of bacterial communities from a 140-cm-long sediment core at 4-cm intervals and detected the critical transition. Our results showed that the historical trajectory of bacterial communities from the 1200 s to the 2010s was divided into two alternative states: state1 from 1200 to 1300 s and state2 from 1400 to 2010s. Furthermore, in the late 1300 s, the appearance of a tipping point and critical slowing down implied the existence of a critical transition. By using a multi-decadal time series from the sedimentary core, with general Lotka-Volterra model simulations, local stability analysis found that bacterial communities were the most unstable as they approached the critical transition, suggesting that the collapse of stability triggers the community shift from an equilibrium state to another state. Furthermore, the most unstable community harbored the strongest antagonistic and mutualistic interactions, which may imply the detrimental role of interaction strength on community stability. Collectively, our study showed that sediment DNA can be used to detect the critical transition of lake ecosystems.

Terpenoids from the Soft Coral Stereonephthya bellissima.

A detailed chemical study of the extract from the soft coral Stereonephthya bellissima resulted in the isolation and identification of seven new sesquiterpenoids, bellissinanes A-G (1-7), along with four new diterpenes (8-11). Bellissinane A (1) is the third reported nardosinane-type sesquiterpene bearing a 6/5/6 tricyclic system. Bellissinanes C and D (3, 4) contain a phenylethylamine fragment, which is relatively unusual in marine organisms. Bellissinanes E-G (5-7) belong to the rare class of nornardosinane sesquiterpenoids. Structurally uncommon octahydro-1H-indenyl-type and prenyleudesmane-type skeletons were characterized for herpetopanone B (8) and bellissimain A (9), respectively. Bellissinane E (5) exhibited in vivo angiogenesis-promoting activity.

Concurrent of compound heterozygous variant of a novel in-frame deletion and the common hypomorphic haplotype in TBX6 and inherited 17q12 microdeletion in a fetus.

BACKGROUND: TBX6, a member of the T-box gene family, encodes the transcription factor box 6 that is critical for somite segmentation in vertebrates. It is known that the compound heterozygosity of disruptive variants in trans with a common hypomorphic risk haplotype (T-C-A) in the TBX6 gene contribute to 10% of congenital scoliosis (CS) cases. The deletion of chromosome 17q12 is a rare cytogenetic abnormality, which often leads to renal cysts and diabetes mellitus. However, the affected individuals often exhibit clinical heterogeneity and incomplete penetrance. METHODS: We here present a Chinese fetus who was shown to have CS by ultrasound examination at 17 weeks of gestation. Trio whole-exome sequencing (WES) was performed to investigate the underlying genetic defects of the fetus. In vitro functional experiments, including western-blotting and luciferase transactivation assay, were performed to determine the pathogenicity of the novel variant of TBX6. RESULTS: WES revealed the fetus harbored a compound heterozygous variant of c.338_340del (p.Ile113del) and the common hypomorphic risk haplotype of the TBX6 gene. In vitro functional study showed the p.Ile113del variant had no impact on TBX6 expression, but almost led to complete loss of its transcriptional activity. In addition, we identified a 1.85 Mb deletion on 17q12 region in the fetus and the mother. Though there is currently no clinical phenotype associated with this copy number variation in the fetus, it can explain multiple renal cysts in the pregnant woman. CONCLUSIONS: This study is the first to report a Chinese fetus with a single amino acid deletion variant and a T-C-A haplotype of TBX6. The clinical heterogeneity of 17q12 microdeletion poses significant challenges for prenatal genetic counseling. Our results once again suggest the complexity of prenatal genetic diagnosis.

Selective degradation of tRNASer(AGY) is the primary driver for mitochondrial seryl-tRNA synthetase-related disease.

Mitochondrial translation is of high significance for cellular energy homeostasis. Aminoacyl-tRNA synthetases (aaRSs) are crucial translational components. Mitochondrial aaRS variants cause various human diseases. However, the pathogenesis of the vast majority of these diseases remains unknown. Here, we identified two novel SARS2 (encoding mitochondrial seryl-tRNA synthetase) variants that cause a multisystem disorder. c.654-14T > A mutation induced mRNA mis-splicing, generating a peptide insertion in the active site; c.1519dupC swapped a critical tRNA-binding motif in the C-terminus due to stop codon readthrough. Both mutants exhibited severely diminished tRNA binding and aminoacylation capacities. A marked reduction in mitochondrial tRNASer(AGY) was observed due to RNA degradation in patient-derived induced pluripotent stem cells (iPSCs), causing impaired translation and comprehensive mitochondrial function deficiencies. These impairments were efficiently rescued by wild-type SARS2 overexpression. Either mutation caused early embryonic fatality in mice. Heterozygous mice displayed reduced muscle tissue-specific levels of tRNASers. Our findings elucidated the biochemical and cellular consequences of impaired translation mediated by SARS2, suggesting that reduced abundance of tRNASer(AGY) is a key determinant for development of SARS2-related diseases.

Establishment and pathophysiological evaluation of a novel model of acute compartment syndrome in rats.

BACKGROUND: Researches have used intra-compartmental infusion and ballon tourniquest to create high intra-compartmental pressure in animal models of Acute Compartment Syndrome (ACS). However, due to the large differences in the modeling methods and the evaluation criteria of ACS, further researches of its pathophysiology and pathogenesis are hindered. Currently, there is no ideal animal model for ACS and this study aimed to establish a reproducible, clinically relevant animal model. METHODS: Blunt trauma and fracture were caused by the free falling of weights (0.5 kg, 1 kg, 2 kg) from a height of 40 cm onto the lower legs of rats, and the application of pressures of 100 mmHg, 200 mmHg, 300 mmHg and 400 mmHg to the lower limbs of rats using a modified pressurizing device for 6 h. The intra-compartmental pressure (ICP) and the pressure change (ΔP) of rats with single and combined injury were continuously recorded, and the pathophysiology of the rats was assessed based on serum biochemistry, histological and hemodynamic changes. RESULTS: The ΔP caused by single injury method of different weights falling onto the lower leg did not meet the diagnosis criteria for ACS (< 30 mmHg). On the other hand, a combined injury method of a falling weight of 1.0 kg and the use of a pressurizing device with pressure of 300 mmHg or 400 mmHg for 6 h resulted in the desired ACS diagnosis criteria with a ΔP value of less than 30 mmHg. The serum analytes, histological damage score, and fibrosis level of the combined injury group were significantly increased compared with control group, while the blood flow was significantly decreased compared with control group. CONCLUSION: We successfully established a new preclinical ACS-like rat model, by the compression of the lower leg of rats with 300 mmHg pressure for 6 h and blunt trauma by 1.0 kg weight falling.

Suberitolactams A-D and Suberitopyridines A-B: New γ-lactam and Pyridine Alkaloids Isolated from the South China Sea Sponge Pseudospongosorites suberitoides.

Four new γ-lactam alkaloids, suberitolactams A-D (1-4), two new pyridine alkaloids, suberitopyridines A-B (7-8), and two known compounds (5-6) were isolated from the South China Sea sponge Pseudospongosorites suberitoides. The structures were elucidated by detailed 1D and 2D NMR experiments along with HRESIMS analysis and single crystal X-ray diffraction. Compounds 1 and 8 showed moderate to weak antiviral activity against H1 N1 virus with IC50 values of 27.6 and 13.3 µM, respectively.

Plant species diversity and functional diversity relations in the degradation process of desert steppe in an arid area of northwest China.

Species and functional diversity play a major role in the stability and sustainability of grassland ecosystems. However, changes in species and functional diversity during grassland degradation in arid areas as well as the underlying mechanisms remain unclear. In this study, we surveyed the vegetation and soil properties of arid regions across a degradation gradient to explore the shifts in species and functional diversity in plant communities, their relationships and key determinants during desert steppe degradation. Our results found significant variability in species diversity and functional diversity across degradation stages. Species diversity (Shannon-Wiener index (H), and Pielou index) and functional diversity (functional evenness (FEve) index, and Rao's quadratic entropy (RaoQ) index) tended to increase initially and then decrease with increasing grassland degradation. The Patrick index, Simpson index, functional richness (FRic) index, functional divergence (FDiv) index, and functional dispersion (FDis) index declined as grassland degradation increased. The relationships between species diversity and functional diversity indices at different stages of degradation in the desert steppe were inconsistent. From no to heavy degradation grasslands, the correlation between species diversity and functional diversity gradually weakened. Specifically, there was a significant correlation between Patrick (R) and FRic indices (R2 > 0.7) on both non-degraded and light degraded grasslands, but there was no significant correlation between R and FRic indices in moderately and heavily degraded grasslands (R2 < 0.7), and R2 gradually decreased. Redundancy analysis and partial least squares path modeling showed that grassland degradation has a significant direct effect on the species diversity and functional diversity. In addition grassland degradation has direct and indirect effects on the species diversity through soil available nitrogen, organic matter and total nitrogen. Functional diversity is directly or indirectly affected by species diversity, soil available nitrogen, organic matter and total nitrogen, soil moisture content, soil bulk density, and pH value. In summary, the relationship between species and functional diversity indices gradually weakened from areas with no degradation to heavy degradation in arid desert grasslands. Our study reveals the patterns and relationships between species diversity and functional diversity throughout the process of grassland degradation, demonstrating a gradual decrease in ecosystem stability and sustainability as degradation advances. Our results have significant implications for the restoration of grassland degradation and the management of ecosystem services in arid steppe regions.

Integrating Transcriptome and Chemical Analyses to Provide Insights into Biosynthesis of Terpenoids and Flavonoids in the Medicinal Industrial Crop Andrographis paniculate and Its Antiviral Medicinal Parts.

Andrographis paniculata is a medicinal plant traditionally used to produce diterpene lactones and flavonoids, which possess various biological activities. Widely distributed in China, India, and other Southeast Asia countries, A. paniculata has become an important economic crop, significantly treating SARS-CoV-2, and is being cultivated on a large scale in southern China. The biosynthesis of active ingredients in A. paniculata are regulated and controlled by genes, but their specific roles are still not fully understood. To further explore the growth regulation factors and utilization of its medicinal parts of this industrial crop, chemical and transcriptome analyses were conducted on the roots, stems, and leaves of A. paniculata to identify the biosynthesis pathways and related candidate genes of the active ingredients. The chemical analysis revealed that the main components of A. paniculata were diterpene lactones and flavonoids, which displayed potential ability to treat SARS-CoV-2 through molecular docking. Moreover, the transcriptome sequencing annotated a total of 40,850 unigenes, including 7962 differentially expressed genes. Among these, 120 genes were involved in diterpene lactone biosynthesis and 60 genes were involved in flavonoid biosynthesis. The expression of diterpene lactone-related genes was the highest in leaves and the lowest in roots, consistent with our content determination results. It is speculated that these highly expressed genes in leaves may be involved in the biosynthesis pathway of diterpenes. Furthermore, two class Ⅰ terpene synthases in A. paniculata transcriptome were also annotated, providing reference for the downstream pathway of the diterpene lactone biosynthesis. With their excellent market value, our experiments will promote the study of the biosynthetic genes for active ingredients in A. paniculata and provide insights for subsequent in vitro biosynthesis.

Diagnostic value of plasma and blood cells metagenomic next-generation sequencing in patients with sepsis.

BACKGROUND: Several studies have investigated the detection of plasma cell-free DNA (cfDNA) using metagenomic next-generation sequencing (mNGS). However, to our knowledge, no study has evaluated the diagnostic value of mNGS detection using blood cells. In this study, we aimed to evaluate the performance of a whole blood mNGS assay which includes the results of plasma and blood cells mNGS detection. METHODS: We selected a panel of seven microorganisms to validate both the plasma and blood cells assay for their limits of detection (LoD), linearity, precision, and robustness to interference. In a multicentered prospective study conducted from January 2021 to April 2022, we tested 253 septic patients with plasma and blood cells mNGS and compared it with blood cultures (BCs). The performance of pathogen detection was compared between mNGS and BCs. RESULTS: The LoD for plasma and blood cells mNGS was 8.3-140 genome equivalents (GE)/mL and 26 to 534 colony-forming units (CFU) or copies/mL, respectively. The inter- and intra-assay reproducibility of both plasma and blood cells mNGS was 100%. Compared to plasma mNGS alone, the sensitivity of whole blood mNGS was increased by 18.04% when using BCs as the standard (67.21% vs 85.25%). Furthermore, the sensitivity of whole blood mNGS in diagnosing bloodstream infections (BSIs) was 85.21%, which was significantly higher than that of BCs (36.09%, P＜0.0001) and plasma mNGS (69.82%; P = 0.0007). Additional analysis showed that blood cells mNGS was able to detect bacteria missed by plasma mNGS, while plasma mNGS was effective at detecting viruses. CONCLUSIONS: Our findings indicate that whole blood mNGS shows great potential as a promising diagnostic technique for BSIs owing to its ability to identify pathogens with higher sensitivity.