Sub-bundle based analysis reveals the role of human optic radiation in visual working memory.

White matter (WM) functional activity has been reliably detected through functional magnetic resonance imaging (fMRI). Previous studies have primarily examined WM bundles as unified entities, thereby obscuring the functional heterogeneity inherent within these bundles. Here, for the first time, we investigate the function of sub-bundles of a prototypical visual WM tract-the optic radiation (OR). We use the 7T retinotopy dataset from the Human Connectome Project (HCP) to reconstruct OR and further subdivide the OR into sub-bundles based on the fiber's termination in the primary visual cortex (V1). The population receptive field (pRF) model is then applied to evaluate the retinotopic properties of these sub-bundles, and the consistency of the pRF properties of sub-bundles with those of V1 subfields is evaluated. Furthermore, we utilize the HCP working memory dataset to evaluate the activations of the foveal and peripheral OR sub-bundles, along with LGN and V1 subfields, during 0-back and 2-back tasks. We then evaluate differences in 2bk-0bk contrast between foveal and peripheral sub-bundles (or subfields), and further examine potential relationships between 2bk-0bk contrast and 2-back task d-prime. The results show that the pRF properties of OR sub-bundles exhibit standard retinotopic properties and are typically similar to the properties of V1 subfields. Notably, activations during the 2-back task consistently surpass those under the 0-back task across foveal and peripheral OR sub-bundles, as well as LGN and V1 subfields. The foveal V1 displays significantly higher 2bk-0bk contrast than peripheral V1. The 2-back task d-prime shows strong correlations with 2bk-0bk contrast for foveal and peripheral OR fibers. These findings demonstrate that the blood oxygen level-dependent (BOLD) signals of OR sub-bundles encode high-fidelity visual information, underscoring the feasibility of assessing WM functional activity at the sub-bundle level. Additionally, the study highlights the role of OR in the top-down processes of visual working memory beyond the bottom-up processes for visual information transmission. Conclusively, this study innovatively proposes a novel paradigm for analyzing WM fiber tracts at the individual sub-bundle level and expands understanding of OR function.

Feasibility study of photon-counting CT for material identification based on YSO/SiPM detector: A proof of concept.

BACKGROUND: Current photon-counting computed tomography (CT) systems utilize semiconductor detectors, such as cadmium telluride (CdTe), cadmium zinc telluride (CZT), and silicon (Si), which convert x-ray photons directly into charge pulses. An alternative approach is indirect detection, which involves Yttrium Orthosilicate (YSO) scintillators coupled with silicon photomultipliers (SiPMs). This presents an attractive and cost-effective option due to its low cost, high detection efficiency, low dark count rate, and high sensor gain. OBJECTIVE: This study aims to establish a comprehensive quantitative imaging framework for three-energy-bin proof-of-concept photon-counting CT based on YSO/SiPM detectors developed in our group using multi-voltage threshold (MVT) digitizers and assess the feasibility of this spectral CT for material identification. METHODS: We developed a proof-of-concept YSO/SiPM-based benchtop spectral CT system and established a pipeline for three-energy-bin photon-counting CT projection-domain processing. The empirical A-table method was employed for basis material decomposition, and the quantitative imaging performance of the spectral CT system was assessed. This evaluation included the synthesis errors of virtual monoenergetic images, electron density images, effective atomic number images, and linear attenuation coefficient curves. The validity of employing A-table methods for material identification in three-energy-bin spectral CT was confirmed through both simulations and experimental studies. RESULTS: In both noise-free and noisy simulations, the thickness estimation experiments and quantitative imaging results demonstrated high accuracy. In the thickness estimation experiment using the practical spectral CT system, the mean absolute error for the estimated thickness of the decomposed Al basis material was 0.014 ± 0.010 mm, with a mean relative error of 0.66% ± 0.42%. Similarly, for the decomposed polymethyl methacrylate (PMMA) basis material, the mean absolute error in thickness estimation was 0.064 ± 0.058 mm, with a mean relative error of 0.70% ± 0.38%. Additionally, employing the equivalent thickness of the basis material allowed for accurate synthesis of 70 keV virtual monoenergetic images (relative error 1.85% ± 1.26%), electron density (relative error 1.81% ± 0.97%), and effective atomic number (relative error 2.64% ± 1.26%) of the tested materials. In addition, the average synthesis error of the linear attenuation coefficient curves in the energy range from 40 to 150 keV was 1.89% ± 1.07%. CONCLUSIONS: Both simulation and experimental results demonstrate the accurate generation of 70 keV virtual monoenergetic images, electron density, and effective atomic number images using the A-table method. Quantitative imaging results indicate that the YSO/SiPM-based photon-counting detector is capable of accurately reconstructing virtual monoenergetic images, electron density images, effective atomic number images, and linear attenuation coefficient curves, thereby achieving precise material identification.

Synergistic enzymatic mechanism of lepidolite leaching enhanced by a mixture of Bacillus mucilaginosus and Bacillus circulans.

Numerous studies have demonstrated that the co-leaching of ores by different silicate bacteria significantly improves the performance of bioleaching systems. Nevertheless, the mechanism of different silicate bacteria synergistically or complementarily enhanced the leaching process of lithium-containing silicate remains unclear. This study discussed the leaching impact of the combined presence of two metabolically distinct silicate bacteria on lepidolite, with the aim of comprehending the synergistic effect resulting from the presence of Bacillus mucilaginosus and Bacillus circulans in the leaching process. The results indicated that the polysaccharides and proteins secreted by bacteria-containing functional groups such as -OH and -COOH, which played an important role in the complex decomposition of ores. Organic acids played the role of acid etching and complexation. Bacillus mucilaginosus and Bacillus circulans exhibited low individual leaching efficiency, primarily due to their weak organic acid secretion. Moreover, the prolific polysaccharide production by Bacillus mucilaginosus led to bacterial aggregation, diminishing contact capability with minerals. Bacillus circulans decomposed the excessive polysaccharides produced by Bacillus mucilaginosus through enzymatic hydrolysis in the co-bioleaching process, providing later nutrient supply for both strains. The symbiosis of the two strains enhanced the synthesis and metabolic capabilities of both strains, resulting in increased organic acid secretion. In addition, protein and humic acid production by Bacillus mucilaginosus intensified, collectively enhancing the leaching efficiency. These findings suggested that the primary metabolic products secreted by different bacterial strains in the leaching process differ. The improvement in bioleaching efficiency during co-leaching was attributed to their effective synergistic metabolism. This work contributes to the construction of an efficient engineering microbial community to improve the efficiency of silicate mineral leaching, and reveals the feasibility of microbial co-culture to improve bioleaching.

Immunogenic cell death inducers for cancer therapy: An emerging focus on natural products.

BACKGROUND: Immunogenic cell death (ICD) is a specific form of regulated cell death induced by a variety of stressors. During ICD, the dying cancer cells release damage-associated molecular patterns (DAMPs), which promote dendritic cell maturation and tumor antigen presentation, subsequently triggering a T-cell-mediated anti-tumor immune response. In recent years, a growing number of studies have demonstrated the potential of natural products to induce ICD and enhance tumor cell immunogenicity. Moreover, there is an increasing interest in identifying new ICD inducers from natural products. PURPOSE: This study aimed to emphasize the potential of natural products and their derivatives as ICD inducers to promote research on using natural products in cancer therapy and provide ideas for future novel immunotherapies based on ICD induction. METHOD: This review included a thorough search of the PubMed, Web of Science, Scopus, and Google Scholar databases to identify natural products with ICD-inducing capabilities. A comprehensive search for clinical trials on natural ICD inducers was also conducted using ClinicalTrials.gov, as well as the approved patents using the Espacenet and CNKI Patent Database. RESULTS: Natural compounds that induce ICD can be categorized into several groups, such as polyphenols, flavonoids, terpenoids, and alkaloids. Natural products can induce the release of DAMPs by triggering endoplasmic reticulum stress, activation of autophagy-related pathways, and reactive oxygen species generation, etc. Ultimately, they activate anti-tumor immune response and improve the efficacy of cancer treatments. CONCLUSION: A growing number of ICD inducers from natural products with promising anti-cancer potential have been identified. The detailed information presented in this review will contribute to the further development of natural ICD inducers and cancer treatment strategies based on ICD-induced responses.

Effect of Abdominal Compression on Total Single-Balloon Enteroscopy Rate: A Randomized Controlled Trial.

OBJECTIVE: To evaluate whether abdominal compression significantly increased the total enteroscopy rate in single-balloon enteroscopy (SBE). METHODS: Consecutive patients who underwent SBE at 2 hospitals were prospectively included between June 1, 2020, and September 30, 2021. They were randomly divided into an abdominal compression group and a non-abdominal compression group with use of sealed envelopes generated by a computer. Total enteroscopy rates were compared between the groups. RESULTS: The study included 200 patients. The total enteroscopy rates were 73% and 16% in the abdominal compression and non-abdominal compression groups, respectively (relative risk, 13.55; 95% CI, 6.79 to 27.00; P<.001). The total enteroscopy rate was higher in the 70 patients who were identified to have undergone no previous abdominal surgery or small intestinal stenosis than in the 32 patients who had undergone such procedures in the abdominal compression group (84% vs 47%; relative risk, 6.08; 95% CI, 2.36 to 15.67; P<.001). Relevant positive findings were not significantly different between the groups (58% vs 45%; P=.07). Binary logistic regression analysis found abdominal compression to be associated with a better total enteroscopy rate (odds ratio, 16.68; 95% CI, 7.92 to 35.15; P<.001), and the presence of previous abdominal surgery or small intestinal stenosis was associated with difficulty in completing the total enteroscopy procedure (odds ratio, 0.26; 95% CI, 0.12 to 0.58; P<.01). CONCLUSION: Abdominal compression significantly increased the total enteroscopy rate in SBE. Complete total enteroscopy may be challenging in patients with a history of abdominal surgery or small intestinal stenosis.

Effects of single and combined contamination of total petroleum hydrocarbons and heavy metals on soil microecosystems: Insights into bacterial diversity, assembly, and ecological function.

Deciphering the impact of single and combined contamination of total petroleum hydrocarbons (TPH) and heavy metals on soil microecosystems is essential for the remediation of contaminated habitats, yet it remains incompletely understood. In this study, we employed high-throughput sequencing to investigate the impact of single TPH contamination, single metal contamination, and their co-contamination on soil microbial diversity, assembly mechanisms, composition, ecological function, and resistome. Our results revealed that contamination led to a reduction in alpha diversity, with single contamination displaying lower diversity compared to co-contamination, depending on the concentration of pollutants. Community beta diversity was primarily driven by turnover rather than nestedness, and narrower ecological niches were detected under pollution conditions. The neutral community model suggested that homogenizing dispersal played a significant role in the community assembly process under single TPH or co-contamination, while homogeneous selection dominated under heavy metals pollution. Procrustes analysis demonstrated a correlation between community composition and functional divergence, while Mantel tests linked this divergence to concentrations of Cr, Cr6+, Pb, and TPH. Interestingly, soils co-polluted with TPH and heavy metals exhibited similar genera, community functions, and resistomes as soils contaminated with only metals, highlighting the significant impact of heavy metals. Ecological functions related to carbon (C), nitrogen (N), and sulfur (S) cycles were enhanced under TPH pollution but impaired under heavy metals stress. These findings enhance our understanding of soil microecosystems subjected to TPH, heavy metals, and their co-contamination, and carry significant implications for environmental microecology and pollutant risk assessment.

Whole-genome transcriptome and DNA methylation dynamics of pre-implantation embryos reveal progression of embryonic genome activation in buffaloes.

BACKGROUND: During mammalian pre-implantation embryonic development (PED), the process of maternal-to-zygote transition (MZT) is well orchestrated by epigenetic modification and gene sequential expression, and it is related to the embryonic genome activation (EGA). During MZT, the embryos are sensitive to the environment and easy to arrest at this stage in vitro. However, the timing and regulation mechanism of EGA in buffaloes remain obscure. RESULTS: Buffalo pre-implantation embryos were subjected to trace cell based RNA-seq and whole-genome bisulfite sequencing (WGBS) to draw landscapes of transcription and DNA-methylation. Four typical developmental steps were classified during buffalo PED. Buffalo major EGA was identified at the 16-cell stage by the comprehensive analysis of gene expression and DNA methylation dynamics. By weighted gene co-expression network analysis, stage-specific modules were identified during buffalo maternal-to-zygotic transition, and key signaling pathways and biological process events were further revealed. Programmed and continuous activation of these pathways was necessary for success of buffalo EGA. In addition, the hub gene, CDK1, was identified to play a critical role in buffalo EGA. CONCLUSIONS: Our study provides a landscape of transcription and DNA methylation in buffalo PED and reveals deeply the molecular mechanism of the buffalo EGA and genetic programming during buffalo MZT. It will lay a foundation for improving the in vitro development of buffalo embryos.

Identification and validation of a DNA methylation-driven gene-based prognostic model for clear cell renal cell carcinoma.

BACKGROUND: Clear cell renal cell carcinoma (ccRCC) is a malignant tumor with heterogeneous morphology and poor prognosis. This study aimed to establish a DNA methylation (DNAm)-driven gene-based prognostic model for ccRCC. METHODS: Reduced representation bisulfite sequencing (RRBS) was performed on the DNA extracts from ccRCC patients. We analyzed the RRBS data from 10 pairs of patient samples to screen the candidate CpG sites, then trained and validated an 18-CpG site model, and integrated the clinical characters to establish a Nomogram model for the prognosis or risk evaluation of ccRCC. RESULTS: We identified 2261 DMRs in the promoter region. After DMR selection, 578 candidates were screened, and was correspondence with 408 CpG dinucleotides in the 450 K array. We collected the DNAm profiles of 478 ccRCC samples from TCGA dataset. Using the training set with 319 samples, a prognostic panel of 18 CpGs was determined by univariate Cox regression, LASSO regression, and multivariate Cox proportional hazards regression analyses. We constructed a prognostic model by combining the clinical signatures. In the test set (159 samples) and whole set (478 samples), the Kaplan-Meier plot showed significant differences; and the ROC curve and survival analyses showed AUC greater than 0.7. The Nomogram integrated with clinicopathological characters and methylation risk score had better performance, and the decision curve analyses also showed a beneficial effect. CONCLUSIONS: This work provides insight into the role of hypermethylation in ccRCC. The targets identified might serve as biomarkers for early ccRCC diagnosis and prognosis biomarkers for ccRCC. We believe our findings have implications for better risk stratification and personalized management of this disease.

Transient ischemic attack induced by pulmonary arteriovenous fistula in a child: A case report.

BACKGROUND: Cerebral ischemic stroke is attributed to paradoxical cerebral embolism. Pulmonary arteriovenous fistula (PAVF) is a rare potential cause of cerebral ischemic stroke, and cerebral ischemic stroke induced by PAVF in children is rare. CASE SUMMARY: We report a case of right PAVF that presented as a transient ischemic attack (TIA) in a 13-year-old boy. The patient underwent embolization therapy and remained clinically stable for 2 years after treatment. CONCLUSION: TIA induced by PAVF in children is rare, lacks typical clinical manifestations, and should not be ignored.

White matter BOLD signals at 7 Tesla reveal visual field maps in optic radiation and vertical occipital fasciculus.

There is growing evidence that blood-oxygen-level-dependent (BOLD) activity in the white matter (WM) can be detected by functional magnetic resonance imaging (fMRI). However, the functional relevance and significance of WM BOLD signals remain controversial. Here we investigated whether 7T BOLD fMRI can reveal fine-scale functional organizations of a WM bundle. Population receptive field (pRF) analyses of the 7T retinotopy dataset from the Human Connectome Project revealed clear contralateral retinotopic organizations of two visual WM bundles: the optic radiation (OR) and the vertical occipital fasciculus (VOF). The retinotopic maps of OR are highly consistent with post-mortem dissections and diffusion tractographies, while the VOF maps are compatible with the dorsal and ventral visual areas connected by the WM. Similar to the grey matter (GM) visual areas, both WM bundles show over-representations of the central visual field and increasing pRF size with eccentricity. Hemodynamic response functions of visual WM were slower and wider compared with those of GM areas. These findings clearly demonstrate that WM BOLD at 7 Tesla is closely coupled with neural activity related to axons, encoding highly specific information that can be used to characterize fine-scale functional organizations of a WM bundle.

A Novel Anti-Osteoporosis Mechanism of VK2: Interfering with Ferroptosis via AMPK/SIRT1 Pathway in Type 2 Diabetic Osteoporosis.

Type 2 diabetic osteoporosis (T2DOP) is a chronic bone metabolic disease. Compared with traditional menopausal osteoporosis, the long-term high glucose (HG) microenvironment increases patients' risk of fracture and osteonecrosis. We were accumulating evidence that implicated ferroptosis as a pivotal mechanism of glucolipotoxicity-mediated death of osteocytes and osteoblast, a novel form of programmed cell death resulting from uncontrolled lipid peroxidation depending on iron. Vitamin K2 (VK2), a fat-soluble vitamin, is clinically applied to prevent osteoporosis and improve coagulation. This study aimed to clarify the role and mechanism of VK2 in HG-mediated ferroptosis. We established the mouse T2DOP model by intraperitoneal injection of streptozotocin solution and a high-fat and high-sugar diet. We also cultured bone marrow mesenchymal stem cells (BMSCs) in HG to simulate the diabetic environment in vitro. Based on our data, VK2 inhibited HG-mediated bone loss and ferroptosis, the latter manifested by decreased levels of mitochondrial reactive oxygen species, lipid peroxidation, and malondialdehyde and increased glutathione in vitro. In addition, VK2 treatment was capable of restoring bone mass and strengthening the expression of SIRT1, GPX4, and osteogenic markers in the distal femurs. As for further mechanism exploration, we found that VK2 could activate AMPK/SIRT1 signaling, and knockdown of SIRT1 by siRNA prevented the VK2-mediated positive effect in HG-cultured BMSCs. Summarily, VK2 could ameliorate T2DOP through the activation of the AMPK/SIRT1 signaling pathway to inhibit ferroptosis.

Covalently connected core-shell NH2-MIL-125@COFs-OH hybrid materials for visible-light-driven CO2 reduction.

Herein, the covalently connected core-shell metal-organic frameworks (MOFs)@covalent-organic frameworks (COFs) hybrid materials were successfully constructed by coating the stable COF-OH shell on the NH2-MIL-125 core. The introduction of the NH2-MIL-125 core endowed the hybrid materials with high Brunauer-Emmett-Teller (BET) surface area (SBET) and abundant unsaturated metal sites. And the coating of COF-OH shell endowed the hybrid materials outstanding physicochemical stability and visible-light response, and suitable band gaps. Moreover, the thickness of the COF-OH shell was carefully adjusted according to the feeding amount of NH2-MIL-125. Impressively, the electron transfer pathway in the formed heterostructure was clarified and it was proven that a type-II heterojunction was generated between the MOFs and the COFs. The formed stable CN covalent bonds in the interfacial layer was beneficial to the photogenerated electron transfer and the electron-hole pairs separation, which greatly enhanced the CO2 photocatalytic reduction. The product NH2-MIL-125@COF-3 exhibited the highest CO yield of 22.93 µmol·g-1·h-1, about 2 times higher than NH2-MIL-125 (11.82 µmol·g-1·h-1) and 3 times greater than COF-OH (7.26 µmol·g-1·h-1). This work can provide helpful ideas for the careful design of the novel MOFs@COFs hybrid materials as well as useful exploration for the CO2 photocatalytic reduction.

Pose-Driven Realistic 2-D Motion Synthesis.

A realistic 2-D motion can be treated as a deforming process of an individual appearance texture driven by a sequence of human poses. In this article, we thereby propose to transform the 2-D motion synthesis into a pose conditioned realistic motion image generation task considering the promising performance of pose estimation technology and generative adversarial nets (GANs). However, the problem is that GAN is only suitable to do the region-aligned image translation task while motion synthesis involves a large number of spatial deformations. To avoid this drawback, we design a two-step and multistream network architecture. First, we train a special GAN to generate the body segment images with given poses in step-I. Then in step-II, we input the body segment images as well as the poses into the multistream network so that it only needs to generate the textures in each aligned body region. Besides, we provide a real face as another input of the network to improve the face details of the generated motion image. The synthesized results with realism and sharp details on four training sets demonstrate the effectiveness of the proposed model.

Coordinated transcriptional and post-transcriptional epigenetic regulation during skeletal muscle development and growth in pigs.

BACKGROUND: N6-methyladenosine (m6A) and DNA 5-methylcytosine (5mC) methylation plays crucial roles in diverse biological processes, including skeletal muscle development and growth. Recent studies unveiled a potential link between these two systems, implicating the potential mechanism of coordinated transcriptional and post-transcriptional regulation in porcine prenatal myogenesis and postnatal skeletal muscle growth. METHODS: Immunofluorescence and co-IP assays were carried out between the 5mC writers and m6A writers to investigate the molecular basis underneath. Large-scale in-house transcriptomic data were compiled for applying weighted correlation network analysis (WGCNA) to identify the co-expression patterns of m6A and 5mC regulators and their potential role in pig myogenesis. Whole-genome bisulfite sequencing (WGBS) and methylated RNA immunoprecipitation sequencing (MeRIP-seq) were performed on the skeletal muscle samples from Landrace pigs at four postnatal growth stages (days 30, 60, 120 and 180). RESULTS: Significantly correlated expression between 5mC writers and m6A writers and co-occurrence of 5mC and m6A modification were revealed from public datasets of C2C12 myoblasts. The protein-protein interactions between the DNA methylase and the m6A methylase were observed in mouse myoblast cells. Further, by analyzing transcriptome data comprising 81 pig skeletal muscle samples across 27 developmental stages, we identified a 5mC/m6A epigenetic module eigengene and decoded its potential functions in pre- or post-transcriptional regulation in postnatal skeletal muscle development and growth of pigs. Following integrative multi-omics analyses on the WGBS methylome data and MeRIP-seq data for both m6A and gene expression profiles revealed a genome/transcriptome-wide correlated dynamics and co-occurrence of 5mC and m6A modifications as a consequence of 5mC/m6A crosstalk in the postnatal myogenesis progress of pigs. Last, we identified a group of myogenesis-related genes collaboratively regulated by both 5mC and m6A modifications in postnatal skeletal muscle growth in pigs. CONCLUSIONS: Our study discloses a potential epigenetic mechanism in skeletal muscle development and provides a novel direction for animal breeding and drug development of related human muscle-related diseases.

A Deep Learning Framework for Start-End Frame Pair-Driven Motion Synthesis.

A start-end frame pair and a motion pattern-based motion synthesis scheme can provide more control to the synthesis process and produce content-various motion sequences. However, the data preparation for the motion training is intractable, and concatenating feature spaces of the start-end frame pair and the motion pattern lacks theoretical rationality in previous works. In this article, we propose a deep learning framework that completes automatic data preparation and learns the nonlinear mapping from start-end frame pairs to motion patterns. The proposed model consists of three modules: action detection, motion extraction, and motion synthesis networks. The action detection network extends the deep subspace learning framework to a supervised version, i.e., uses the local self-expression (LSE) of the motion data to supervise feature learning and complement the classification error. A long short-term memory (LSTM)-based network is used to efficiently extract the motion patterns to address the speed deficiency reflected in the previous optimization-based method. A motion synthesis network consists of a group of LSTM-based blocks, where each of them is to learn the nonlinear relation between the start-end frame pairs and the motion patterns of a certain joint. The superior performances in action detection accuracy, motion pattern extraction efficiency, and motion synthesis quality show the effectiveness of each module in the proposed framework.

Local Self-Expression Subspace Learning Network for Motion Capture Data.

Deep subspace learning is an important branch of self-supervised learning and has been a hot research topic in recent years, but current methods do not fully consider the individualities of temporal data and related tasks. In this paper, by transforming the individualities of motion capture data and segmentation task as the supervision, we propose the local self-expression subspace learning network. Specifically, considering the temporality of motion data, we use the temporal convolution module to extract temporal features. To implement the local validity of self-expression in temporal tasks, we design the local self-expression layer which only maintains the representation relations with temporally adjacent motion frames. To simulate the interpolatability of motion data in the feature space, we impose a group sparseness constraint on the local self-expression layer to impel the representations only using selected keyframes. Besides, based on the subspace assumption, we propose the subspace projection loss, which is induced from distances of each frame projected to the fitted subspaces, to penalize the potential clustering errors. The superior performances of the proposed model on the segmentation task of synthetic data and three tasks of real motion capture data demonstrate the feature learning ability of our model.

Glomerular filtration rate calculation based on 68Ga-EDTA dynamic renal PET.

Positron emission tomography (PET) can accurately locate and quantify radioactivity over traditional single photon emission computed tomography (SPECT), encouraging its application in kidney function evaluation and glomerular filtration rate (GFR) measurement. 68Ga-ethylenediamine-tetraacetic acid (68Ga-EDTA) is a novel PET tracer for renal scan but a mature GFR calculation method still pending establishment. Herein, we aim to investigate the imaging performance of 68Ga-EDTA dynamic PET in healthy C57BL/6 mice, establish quantitative methods to calculate GFR, and evaluate its feasibility in mice with kidney dysfunction. Dynamic PET of 68Ga-EDTA successfully visualized the whole process of tracer elimination. GFR values were measured by the integral method (253.80±40.11 µL/min) and the Patlak Plot method (22.69±9.75 µL/min), while blood clearance rate of the tracer was found at 787.46±70.86 µL/min. The PET-based GFR values correlate well with the GFRblood (R2=0.7468, R2=0.8793). The Integral method provides better accuracy than Patlak Plot method. Further application of GFR measurement in kidney-diseased mice proves better performance of the Integral method for defining split renal function.

Longitudinal physiological and transcriptomic analyses reveal the short term and long term response of Synechocystis sp. PCC6803 to cadmium stress.

Due to the bioaccumulation and non-biodegradability of cadmium, Cd can pose a serious threat to ecosystem even at low concentration. Microalgae is widely distributed photosynthetic organisms in nature, which is a promising heavy metal remover and an effective industrial sewage cleaner. However, there are few detailed reports on the short-term and long-term molecular mechanisms of microalgae under Cd stress. In this study, the adsorption behavior (growth curve, Cd removal efficiency, scanning electron microscope, Fourier transform infrared spectroscopy, and dynamic change of extracellular polymeric substances), cytotoxicity (photosynthetic pigment, MDA, GSH, H2O2, O2-) and stress response mechanism of microalgae were discussed under EC50. RNA-seq detected 1413 DEGs in 4 treatment groups. These genes were related to ribosome, nitrogen metabolism, sulfur transporter, and photosynthesis, and which been proved to be Cd-responsive DEGs. WGCNA (weighted gene co-expression network analysis) revealed two main gene expression patterns, short-term stress (381 genes) and long-term stress (364 genes). The enrichment analysis of DEGs showed that the expression of genes involved in N metabolism, sulfur transporter, and aminoacyl-tRNA biosynthesis were significantly up-regulated. This provided raw material for the synthesis of the important component (cysteine) of metal chelate protein, resistant metalloprotein and transporter (ABC transporter) in the initial stage, which was also the short-term response mechanism. Cd adsorption of the first 15 min was primary dependent on membrane transporter and beforehand accumulated EPS. Simultaneously, the up-regulated glutathione S-transferase (GSTs) family proteins played a role in the initial resistance to exogenous Cd. The damaged photosynthetic system was repaired at the later stage, the expressions of glycolysis and gluconeogenesis were up-regulated, to meet the energy and substances of physiological metabolic activities. The study is the first to provide detailed short-term and long-term genomic information on microalgae responding to Cd stress. Meanwhile, the key genes in this study can be used as potential targets for algae-mediated genetic engineering.

Potential roles of vitamin D binding protein in attenuating liver injury in sepsis.

BACKGROUND: In sepsis, vitamin D binding protein (VDBP) has been shown to be low-expressed. The current study examined the relationship between serum VDBP level and liver injury in sepsis patients, as well as in a mouse model for sepsis and in cultured liver epithelial cell line exposed to lipopolysaccharide (LPS). METHODS: The human study included 78 sepsis patients and 50 healthy volunteers. Sepsis patients were categorized into sepsis survivor group (n = 43) and sepsis non-survivor group (n = 35) based on 28-day mortality for data analysis. Adult male C57BL/6 mice were subjected to cecal ligation and puncture (CLP). Serum samples were collected on day 1, 3, 5 and 7 to determine the levels of VDBP, 25-hydroxyvitamin D [25(OH)D3], 1,25-dihydroxyvitamin D [1,25(OH)2D3], interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-α). Potential protective effects of VDBP overexpression against LPS-induced liver damage were examined in cultured THLE2 cells. RESULTS: Serum levels of VDBP, 25(OH)D3, and 1,25(OH)2D3 were significantly lower in sepsis patients vs. the healthy control (P < 0.001), as well as in the sepsis non-survivor group vs. the sepsis survivor group (P < 0.001, P = 0.0338, or P = 0.0013, respectively). Lower serum VDBP level was associated with higher Acute Physiology and Chronic Health Evaluation (APACHE) II score (r = - 0.2565, P = 0.0234) and Sequential Organ Failure Assessment score (r = - 0.3522, P = 0.0016), but lower serum albumin (ALB, r = 0.4628, P < 0.001) and total protein (TP, r = 0.263, P = 0.02). In CLP mice, there was a 5-day period of serum VDBP reduction, followed by return towards the baseline on day 7. VDBP was also decreased in LPS-treated THLE2 cells (P < 0.001). VDBP overexpression reduced LPS-induced THLE2 damage. Reduced damage was associated with decreased oxidative stress and inactivation of the c-Jun N-terminal kinase signaling pathway. CONCLUSION: VDBP may be protective against sepsis-induced liver injury.