Biologically generated turbulent energy flux in shear flow depends on tensor geometry.

It has been proposed that biologically generated turbulence plays an important role in material transport and ocean mixing. Both experimental and numerical studies have reported evidence of the nonnegligible mixing by moderate Reynolds number swimmers, such as zooplankton, in quiescent water, especially at aggregation scales. However, the interaction between biologically generated agitation and the background flow, as a key factor in biologically generated turbulence that could reshape our previous knowledge of biologically generated turbulence, has long been ignored. Here, we show that the geometry between the biologically generated agitation and the background hydrodynamic shear can determine both the intensity and direction of biologically generated turbulent energy flux. Measuring the migration of a centimeter-scale swimmer-as represented by the brine shrimp Artemia salina-in a shear flow and verifying through an analog experiment with an artificial jet revealed that different geometries between the biologically generated agitation and the background shear can result in spectral energy transferring toward larger or smaller scales, which consequently intensifies or attenuates the large-scale hydrodynamic shear. Our results suggest that the long ignored geometry between the biologically generated agitation and the background flow field is an important factor that should be taken into consideration in future studies of biologically generated turbulence.

Epidemiological and molecular investigations of sequential outbreaks of Campylobacter jejuni infecting adults and schoolchildren in southeastern China, 2021-2022.

OBJECTIVES: To investigate cases of five Campylobacter jejuni outbreaks and describe laboratory characteristics of these infections. METHODS: Whole genome sequencing and conventional methods were combined to thoroughly investigate the outbreaks, and data of contemporaneous sporadic cases was included for comparison. RESULTS: Seven sequence types (ST) of C. jejuni caused 83 cases, including ST9079 which recurred across two years. Trace-back investigation could not identify any food items of infection, but detected identical campylobacters from food contacts. Phylogenetic analysis unveiled genetic closeness between outbreak strains and some concurrent sporadic strains, indicating local campylobacteriosis may not be wholly sporadic but rather a series of linked cases. Virulence genes disclosed species/case-specific signatures to differentiate outbreak from truly non-outbreak strains. Resistance to fluoroquinolones and/or macrolides was prevalent (90.8%, 108/119), with a noteworthy portion exhibiting multidrug resistance (31.1%, 37/119). Five types of plasmids were harbored among outbreak isolates, which one plasmid harboring anti-stress and resistant genes was rarely found in C. jejuni. CONCLUSIONS: This is the first reported sequential outbreaks of C. jejuni in China. Our observations help to define the genomic landscape and antimicrobial resistance patterns of Campylobacter, emphasizing the need for a broader 'One Health' perspective to combat the threats posed by campylobacteriosis.

Insight into the probability of ethoxy(pentafluoro)cyclotriphosphazene (PFPN) as the functional electrolyte additive in lithium-sulfur batteries.

Enhancing the flame retardancy of electrolytes and the stability of lithium anodes is of great significance to improve the safety performance of lithium-sulfur (Li-S) batteries. It is well known that the most commonly used ether based electrolyte solvents in Li-S batteries have a lower flash point and higher volatility than the ester electrolyte solvents in Li-ion batteries. Hence, lithium-sulfur batteries have greater safety risks than lithium-ion batteries. Herein, ethoxy(pentafluoro)cyclotriphosphazene (PFPN), which is commonly used as a flame retardant for ester electrolytes in lithium-ion batteries, is utilized as both a film-forming electrolyte additive and a flame retardant additive for the ether electrolyte to investigated its applicability in Li-S batteries. It is found that the ether electrolyte containing PFPN not only has good flame retardant properties and a wide potential window of about 5 V, but also can form a stable SEI film on the surface of a lithium anode. As a result, with the ether-based electrolyte containing 10 wt% PFPN, Li-Cu and Li-S batteries all delivered a stable cycling performance with a high coulombic Efficiency and a long-lifespan performance, which were all superior to the batteries using the ether-based electrolyte without PFPN. This study demonstrates an effective solution to solve the problems of flammable ether-based electrolytes and reactive lithium anodes, and it may contribute to the development of safe Li-S batteries.

Heat-Induced Secretion of Heat Shock Proteins 70 and 90 Does not Affect the Expression of the Glucocorticoid Receptor in Primary Airway Cells in COPD.

PURPOSE: The response to glucocorticoids is hampered in many COPD patients by a yet unknown mechanism. Earlier we reported that short-term heat exposure of primary human bronchial epithelial cells (BEC) and airway smooth muscle cells (ASMC) of asthma patients increased the expression and secretion of extracellular heat shock proteins (eHSPs) resulting in increased expression of glucocorticoid receptor (GR) in BEC and inhibition of ASMC remodeling. The aim of the present study was to assess if the same mechanism is also present in primary airway wall cells of COPD patients. METHODS: Primary BEC and ASMC were established from endobronchial biopsies obtained from COPD patients (n = 73), who participated in the HISTORIC study, an investigator-initiated and driven clinical trial. Secretion and protein expression of HSPs was assessed by ELISA and Western blotting. Expression of total GR, its isoforms GRα and GRß and toll-like receptor 4 (TLR4) was determined by Western-blotting. RESULTS: Short heat exposure (65 °C, 10 s) of BEC resulted in a significant increase of the secretion of eHSP70 and eHSP90, while the intracellular protein was not altered. Heat treatment or exposure to eHSP70 or eHSP90 had no effect on the expression of GR and GR-isoforms. However, eHSP70 and eHSP90 significantly reduced the expression of TLR4. CONCLUSIONS: The results of this study indicate that primary airway cells from COPD patients respond differently to heat exposure and extracellular HSP70 or HSP90 than cells from asthma patients regarding the expression of GR and this may explain the reduced response to glucocorticoids in patients with COPD. TRIAL REGISTRATION: ISRCTN11017699.

Small extracellular vesicles from young plasma reverse age-related functional declines by improving mitochondrial energy metabolism.

Recent investigations into heterochronic parabiosis have unveiled robust rejuvenating effects of young blood on aged tissues. However, the specific rejuvenating mechanisms remain incompletely elucidated. Here we demonstrate that small extracellular vesicles (sEVs) from the plasma of young mice counteract pre-existing aging at molecular, mitochondrial, cellular and physiological levels. Intravenous injection of young sEVs into aged mice extends their lifespan, mitigates senescent phenotypes and ameliorates age-associated functional declines in multiple tissues. Quantitative proteomic analyses identified substantial alterations in the proteomes of aged tissues after young sEV treatment, and these changes are closely associated with metabolic processes. Mechanistic investigations reveal that young sEVs stimulate PGC-1α expression in vitro and in vivo through their miRNA cargoes, thereby improving mitochondrial functions and mitigating mitochondrial deficits in aged tissues. Overall, this study demonstrates that young sEVs reverse degenerative changes and age-related dysfunction, at least in part, by stimulating PGC-1α expression and enhancing mitochondrial energy metabolism.

Evolutionary trends and analysis of the driving factors of Ulva prolifera green tides: A study based on the random forest algorithm and multisource remote sensing images.

Understanding the prolonged spatiotemporal evolution and identifying the underlying causes of Ulva prolifera green tides play pivotal roles in managing such occurrences, restoring water ecology, and fostering sustainable development in marine ecosystems. Satellite remote sensing represents the primary choice for monitoring Ulva prolifera green tides due to its capability for extensive, long-term ocean monitoring. Based on multi-source remote sensing images, ecological and environmental datasets, and machine learning algorithms, therefore, this study focused on "remote sensing modelling - evolution history - change trends - mechanism analysis" to elucidate both the remote sensing monitoring models and the underlying driving factors governing the spatiotemporal evolution of Ulva prolifera green tides in the highly impacted South Yellow Sea of China. With the use of GOCI Ⅰ/Ⅱ images, an hybrid remote sensing extraction model merging the robustness of the random forest (RF) model and the optical algae cloud index (ACI) was established to map Ulva prolifera distribution patterns. The ACI-RF method exhibited exceptional performance, with an F1 score surpassing 0.95, outperforming alternative methods such as the support vector machine (SVM) and K-nearest neighbour (KNN) methods. On the basis, we analysed the evolutionary trends and the driving factors determining these distribution patterns using meteorological data, runoff data, and data on various water quality parameters (SST, ocean current speed, wind speed, precipitation, DO, PAR, Si, NO3-, PO43-and N/P). Over the period from 2011 to 2022, excluding 2021, there was a notable decline in the area of Ulva prolifera green tides, varying between 397 and 2689.9 km2, with an average annual reduction rate of 3%. The maximum annual biomass varied between 0.12 and 15.9 kt. Notably, more than 75% of the area of Ulva prolifera green tides exhibited northward drift, which was significantly influenced by northern currents and wind fields. The analysis of driving factors indicates that factors such as average sea surface temperature, eastward wind speed, northward wind speed, precipitation, PO43- and N/P/Si significantly influence the biological growth rate of Ulva prolifera. Furthermore, coastal land use change and surface runoff, particularly surface runoff in June, significantly impacted the growth rate of Ulva prolifera, with Pearson correlation coefficients of 0.74 and 0.67, respectively. Against the background of global warming and severe deterioration in the marine environment, Ulva prolifera blooms persist. Consequently, two distinct management strategies were proposed based on the distribution patterns and cause analysis results for addressing Ulva prolifera green tides: establishing a continuous protection framework for rivers, lakes, and nearshore areas to mitigate pollutant inputs and implementing precise environmental monitoring measures in urban expansion areas and farmlands to combat overgrowth-induced green tides. This methodology could be applied in other regions affected by marine ecological disasters, and the criteria for selecting influencing factors offer a valuable reference for designing tailored and proactive measures aimed at controlling Ulva prolifera green tides.

Folate-PEG-PROTAC Micelles for Enhancing Tumor-Specific Targeting Proteolysis In Vivo.

Proteolysis targeting chimeras (PROTACs) technology is rapidly developed as a novel and selective medicinal strategy for the degradation of cellular proteins in cancer therapy. However, the applications of PROTACs as heterobifunctional molecules are largely limited by high molecular weight, low bioavailability, poor permeability, insufficient targeting, and low efficacy in vivo. Herein, self-assembling micelles of FA-PEG-PROTAC are designed for cancer cell selective targeting and reductive-response proteolysis in tumor-bearing mice. FA-PEG-PROTAC is prepared by conjugating folic acid (FA)-PEG with EGFR-targeting PROTAC via a disulfide bond. The FA-PEG-PROTAC micelles, formed by self-assembling, are demonstrated to significantly improve tumor targeting efficacy and exhibit excellent anti-tumor efficacy in the mouse xenograft model compared to the traditional PROTACs. The strategy of applying self-assembled FA-PEG-PROTAC micelles in tumor therapy can not only improve targeted proteolysis efficiency but also broaden applications in the development of PROTAC-based drugs.

The characterization of protein lactylation in relation to cardiac metabolic reprogramming in neonatal mouse hearts.

In mammals, the neonatal heart can regenerate upon injury within a short time after birth, while adults lose this ability. Metabolic reprogramming has been demonstrated to be critical for cardiomyocyte proliferation in the neonatal heart. Here, we reveal that cardiac metabolic reprogramming could be regulated by altering global protein lactylation. By performing 4D label-free proteomics and lysine lactylation (Kla) omics analyses in mouse hearts at postnatal days 1, 5, and 7, 2297 Kla sites from 980 proteins are identified, among which 1262 Kla sites from 409 proteins are quantified. Functional clustering analysis reveals that the proteins with altered Kla sites are mainly involved in metabolic processes. The expression and Kla levels of proteins in glycolysis show a positive correlation while a negative correlation in fatty acid oxidation. Furthermore, we verify the Kla levels of several differentially modified proteins, including ACAT1, ACADL, ACADVL, PFKM, PKM, and NPM1. Overall, our study reports a comprehensive Kla map in the neonatal mouse heart, which will help to understand the regulatory network of metabolic reprogramming and cardiac regeneration.

A large-scale survey of urinary parabens and triclocarban in the Chinese population as well as the influencing factors and health risks.

Parabens and triclocarban are widely applied as antimicrobial preservatives in foodstuffs, pharmaceuticals, cosmetics, and personal care products. However, few studies have been conducted on large-scale biomonitoring of parabens and triclocarban in the Chinese general population. In the present study, there were 1157 urine samples collected from 26 Chinese provincial capitals for parabens and triclocarban measurement to evaluate the exposure levels, spatial distribution, and influencing factors, as well as associated health risks in the Chinese population. The median concentrations of Σparabens and triclocarban were 14.0 and 0.03 µg/L, respectively. Methyl paraben was the predominant compound. Subjects in western China were more exposed to parabens, possibly due to climate differences resulting in higher consumption of personal care products. Subjects who were female, aged 18-44 years, or had a higher education level were found to have higher paraben concentrations. The frequency of drinking bottled water was positively associated with paraben exposure. The assessment of health risk based on urinary paraben concentrations indicated that 0.8 % of the subjects had a hazard index exceeding one unit, while Monte Carlo analysis suggested that 3.6 % of the Chinese population exposure to parabens had a potential non-carcinogenic risk. This large-scale biomonitoring study will help to understand the exposure levels of parabens and triclocarban in the Chinese general population and provide supporting information for government decision-making.

Effect of solvent quality and sidechain architecture on conjugated polymer chain conformation in solution.

Conjugated polymers (CPs) are solution-processible for various electronic applications, where solution aggregation and dynamics could impact the morphology in the solid state. Various solvents and solvent mixtures have been used to dissolve and process CPs, but few studies have quantified the effect of solvent quality on the solution behavior of CPs. Herein, we performed static light scattering and small-angle X-ray scattering combined with molecular dynamics (MD) simulation to investigate CP solution behaviors with solvents of varying quality, including poly(3-alkylthiophene) (P3ATs) with various sidechain lengths from -C4H9 to -C12H25, poly[bis(3-dodecyl-2-thienyl)-2,2'-dithiophene-5,5'-diyl] (PQT-12) and poly[2,5-bis(3-dodecylthiophen-2-yl)thieno[3,2-b]thiophene] (PBTTT-12). We found that chlorobenzene is a better solvent than toluene for various CPs, which was evident from the positive second virial coefficient A2 ranging from 0.3 to 4.7 × 10-3 cm3 mol g-2 towards P3ATs. For P3ATs in non-polar solvents, longer sidechains promote more positive A2, indicating a better polymer-solvent interaction, wherein A2 for toluene increases from -5.9 to 1.4 × 10-3 cm3 mol g-2, and in CB, A2 ranges from 1.0 to 4.7 × 10-3 cm3 mol g-2 when sidechain length increases from -C6H13 to -C12H25. Moreover, PQT-12 and PBTTT-12 have strong aggregation tendencies in all solutions, with an apparent positive A2 (∼0.5 × 10-3 cm3 mol g-2) due to multi-chain aggregates and peculiar chain folding. These solvent-dependent aggregation behaviors can be well correlated to spectroscopy measurement results. Our coarse-grained MD simulation results further suggested that CPs with long, dense, and branched sidechains can achieve enhanced polymer-solvent interaction, and thus enable overall better solution dispersion. This work provides quantitative insights into the solution behavior of conjugated polymers that can guide both the design and process of CPs toward next-generation organic electronics.

Decreased plasma miR-140-3p is associated with coronary artery disease.

Background: Although many circulating miRNAs (c-miRNAs) are associated with coronary artery disease (CAD), they are far from being the biomarker for CAD diagnosis or risk prediction. Therefore, novel c-miRNAs discovery and validation are still required, especially evaluating their prediction capacity. Objectives: Identify novel CAD-related c-miRNAs and evaluate its risk prediction capacity for CAD. Methods: miRNAs associated with CAD were preliminarily investigated in three paired samples representing pre-CAD stage and CAD stage of three female individuals using the Applied Biosystems miRNA TaqMan® Low-Density Array (TLDA). Then, the candidate miRNAs were further verified in an independent case-control study including 129 CAD patients and 76 controls, and their potential practical value in prediction for CAD was evaluated using a machine learning (ML) algorithm. The accuracy of classification and prediction was assessed with the area under the receiver operating characteristic curve (AUC). Results: TLDA analysis shows that miR-140-3p decreased significantly in CAD-stage (FC = -3.01, P = 0.007). Further study shows that miR-140-3p was significantly lower in CAD group [1.26 (0.68, 2.01)] than in control group [2.07 (1.19, 3.21)] (P < 0.001) and independently associated with CAD (P < 0.001). The addition of miR-140-3p to the variables including smoking history, HDL-c, and APOA1 improved the accuracy of classification by logistic regression and of prediction for CAD by ML models. The ML models built with miR-140-3p and HDL-c, respectively, had a similar prediction accuracy. The feature importance of miR-140-3p and HDL-c in the ML models was also similar. Decision curve analysis showed that miR-140-3p and HDL-c had almost identical net benefits. Conclusion: Reduced levels of miR-140-3p is linked to CAD, and it is possible to use the plasma level of miR-140-3p as a means of evaluating the risk of CAD.

AMPK phosphorylation of FNIP1 (S220) controls mitochondrial function and muscle fuel utilization during exercise.

Exercise-induced activation of adenosine monophosphate-activated protein kinase (AMPK) and substrate phosphorylation modulate the metabolic capacity of mitochondria in skeletal muscle. However, the key effector(s) of AMPK and the regulatory mechanisms remain unclear. Here, we showed that AMPK phosphorylation of the folliculin interacting protein 1 (FNIP1) serine-220 (S220) controls mitochondrial function and muscle fuel utilization during exercise. Loss of FNIP1 in skeletal muscle resulted in increased mitochondrial content and augmented metabolic capacity, leading to enhanced exercise endurance in mice. Using skeletal muscle-specific nonphosphorylatable FNIP1 (S220A) and phosphomimic (S220D) transgenic mouse models as well as biochemical analysis in primary skeletal muscle cells, we demonstrated that exercise-induced FNIP1 (S220) phosphorylation by AMPK in muscle regulates mitochondrial electron transfer chain complex assembly, fuel utilization, and exercise performance without affecting mechanistic target of rapamycin complex 1-transcription factor EB signaling. Therefore, FNIP1 is a multifunctional AMPK effector for mitochondrial adaptation to exercise, implicating a mechanism for exercise tolerance in health and disease.

High-quality genomes of Bombax ceiba and Ceiba pentandra provide insights into the evolution of Malvaceae species and differences in their natural fiber development.

Members of the Malvaceae family, including Corchorus spp., Gossypium spp., Bombax spp., and Ceiba spp., are important sources of natural fibers. In the past decade, the genomes of several Malvaceae species have been assembled; however, the evolutionary history of Malvaceae species and the differences in their fiber development remain to be clarified. Here, we report the genome assembly and annotation of two natural fiber plants from the Malvaceae, Bombax ceiba and Ceiba pentandra, whose assembled genome sizes are 783.56 Mb and 1575.47 Mb, respectively. Comparative analysis revealed that whole-genome duplication and Gypsy long terminal repeat retroelements have been the major causes of differences in chromosome number (2n = 14 to 2n = 96) and genome size (234 Mb to 2676 Mb) among Malvaceae species. We also used comparative genomic analyses to reconstruct the ancestral Malvaceae karyotype with 11 proto-chromosomes, providing new insights into the evolutionary trajectories of Malvaceae species. MYB-MIXTA-like 3 is relatively conserved among the Malvaceae and functions in fiber cell-fate determination in the epidermis. It appears to perform this function in any tissue where it is expressed, i.e. in fibers on the endocarp of B. ceiba and in ovule fibers of cotton. We identified a structural variation in a cellulose synthase gene and a higher copy number of cellulose synthase-like genes as possible causes of the finer, less spinnable, weaker fibers of B. ceiba. Our study provides two high-quality genomes of natural fiber plants and offers insights into the evolution of Malvaceae species and differences in their natural fiber formation and development through multi-omics analysis.

Difference analysis and characteristics of incompatibility group plasmid replicons in gram-negative bacteria with different antimicrobial phenotypes in Henan, China.

BACKGROUND: Multi-drug-resistant organisms (MDROs) in gram-negative bacteria have caused a global epidemic, especially the bacterial resistance to carbapenem agents. Plasmid is the common vehicle for carrying antimicrobial resistance genes (ARGs), and the transmission of plasmids is also one of the important reasons for the emergence of MDROs. Different incompatibility group plasmid replicons are highly correlated with the acquisition, dissemination, and evolution of resistance genes. Based on this, the study aims to identify relevant characteristics of various plasmids and provide a theoretical foundation for clinical anti-infection treatment. METHODS: 330 gram-negative strains with different antimicrobial phenotypes from a tertiary hospital in Henan Province were included in this study to clarify the difference in incompatibility group plasmid replicons. Additionally, we combined the information from the PLSDB database to elaborate on the potential association between different plasmid replicons and ARGs. The VITEK mass spectrometer was used for species identification, and the VITEK-compact 2 automatic microbial system was used for the antimicrobial susceptibility test (AST). PCR-based replicon typing (PBRT) detected the plasmid profiles, and thirty-three different plasmid replicons were determined. All the carbapenem-resistant organisms (CROs) were tested for the carbapenemase genes. RESULTS: 21 plasmid replicon types were detected in this experiment, with the highest prevalence of IncFII, IncFIB, IncR, and IncFIA. Notably, the detection rate of IncX3 plasmids in CROs is higher, which is different in strains with other antimicrobial phenotypes. The number of plasmid replicons they carried increased with the strain resistance increase. Enterobacterales took a higher number of plasmid replicons than other gram-negative bacteria. The same strain tends to have more than one plasmid replicon type. IncF-type plasmids tend to be associated with MDROs. Combined with PLSDB database analysis, IncFII and IncX3 are critical platforms for taking blaKPC-2 and blaNDM. CONCLUSIONS: MDROs tend to carry more complex plasmid replicons compared with non-MDROs. The plasmid replicons that are predominantly prevalent and associated with ARGs differ in various species. The wide distribution of IncF-type plasmids and their close association with MDROs should deserve our attention. Further investigation into the critical role of plasmids in the carriage, evolution, and transmission of ARGs is needed.

Instant mucus dressing of PEO reinforced by chitosan nanofiber scaffold for open wound healing.

Dressings seamlessly attached to the open wound bed are necessary for fully unleashing the dressing healing ability, as leaving the voids beneath the dressing poses infection hazards. The present study prepared an instant mucus dressing (IMD) of polyethylene oxide (PEO) reinforced by chitosan (CS) nanofiber scaffold, which formed by immersing PEO/CS nanofiber mat in water. The PEO/CS nanofiber mat were fabricated by the solution blow spinning (SBS) method using PEO and CS mixed solutions. Attenuated total reflection Fourier transform infrared spectroscopy (FTIR-ATR), transmission electron microscope (TEM), X-ray photoelectron spectroscopy (XPS), X-ray diffraction (XRD) and differential scan calorimetry (DSC) analyses indicate that PEO macromolecules formed the most of nanofiber shell due to their lower surface tension while CS macromolecules stayed mainly inside the fiber as the core. When such a PEO/CS nanofiber mat was immersed in water, PEO swelled to form mucus dressing reinforced by CS inside the nanofiber, which was fluidic and able to fully fill the voids on the wound. In vivo rat experiment verified that the dressing significantly accelerated the open wound healing through seamlessly attaching of mucus to the open wound and providing moist environment. The dressings exhibit good platelets and whole blood cells adhesion properties, excellent hemostasis function and no cytotoxicity. This instant mucus dressing provided a new perspective for manufacturing high performance open wound dressings.

LumVertCancNet: A novel 3D lumbar vertebral body cancellous bone location and segmentation method based on hybrid Swin-transformer.

Lumbar vertebral body cancellous bone location and segmentation is crucial in an automated lumbar spine processing pipeline. Accurate and reliable analysis of lumbar spine image is expected to advantage practical medical diagnosis and population-based analysis of bone strength. However, the design of automated algorithms for lumbar spine processing is demanding due to significant anatomical variations and scarcity of publicly available data. In recent years, convolutional neural network (CNN) and vision transformers (Vits) have been the de facto standard in medical image segmentation. Although adept at capturing global features, the inherent bias of locality and weight sharing of CNN constrains its capacity to model long-range dependency. In contrast, Vits excel at long-range dependency modeling, but they may not generalize well with limited datasets due to the lack of inductive biases inherent to CNN. In this paper, we propose a deep learning-based two-stage coarse-to-fine solution to address the problem of automatic location and segmentation of lumbar vertebral body cancellous bone. Specifically, in the first stage, a Swin-transformer based model is applied to predict the heatmap of lumbar vertebral body centroids. Considering the characteristic anatomical structure of lumbar spine, we propose a novel loss function called LumAnatomy loss, which enforces the order and bend of the predicted vertebral body centroids. To inherit the excellence of CNN and Vits while preventing their respective limitations, in the second stage, we propose an encoder-decoder network to segment the identified lumbar vertebral body cancellous bone, which consists of two parallel encoders, i.e., a Swin-transformer encoder and a CNN encoder. To enhance the combination of CNNs and Vits, we propose a novel multi-scale attention feature fusion module (MSA-FFM), which address issues that arise when fusing features given at different encoders. To tackle the issue of lack of data, we raise the first large-scale lumbar vertebral body cancellous bone segmentation dataset called LumVBCanSeg containing a total of 185 CT scans annotated at voxel level by 3 physicians. Extensive experimental results on the LumVBCanSeg dataset demonstrate the proposed algorithm outperform other state-of-the-art medical image segmentation methods. The data is publicly available at: https://zenodo.org/record/8181250. The implementation of the proposed method is available at: https://github.com/sia405yd/LumVertCancNet.

Integrating Photoactive Ligands into Crystalline Ultrathin 2D Metal-Organic Framework Nanosheets for Efficient Photoinduced Energy Transfer.

3D metal-organic frameworks (MOFs) have gained attention as heterogeneous photocatalysts due to their porosity and unique host-guest interactions. Despite their potential, MOFs face challenges, such as inefficient mass transport and limited light penetration in photoinduced energy transfer processes. Recent advancements in organic photocatalysis have uncovered a variety of photoactive cores, while their heterogenization remains an underexplored area with great potential to build MOFs. This gap is bridged by incorporating photoactive cores into 2D MOF nanosheets, a process that merges the realms of small-molecule photochemistry and MOF chemistry. This approach results in recyclable heterogeneous photocatalysts that exhibit an improved mass transfer efficiency. This research demonstrates a bottom-up synthetic method for embedding photoactive cores into 2D MOF nanosheets, successfully producing variants such as PCN-641-NS, PCN-643-NS, and PCN-644-NS. The synthetic conditions were systematically studied to optimize the crystallinity and morphology of these 2D MOF nanosheets. Enhanced host-guest interactions in these 2D structures were confirmed through various techniques, particularly solid-state NMR studies. Additionally, the efficiency of photoinduced energy transfer in these nanosheets was evidenced through photoborylation reactions and the generation of reactive oxygen species (ROS).

Application scenario-oriented molecule generation platform developed for drug discovery.

Design of molecules for candidate compound selection is one of the central challenges in drug discovery due to the complexity of chemical space and requirement of multi-parameter optimization. Here we present an application scenario-oriented platform (ID4Idea) for molecule generation in different scenarios of drug discovery. This platform utilizes both library or rule based and generative based algorithms (VAE, RNN, GAN, etc.), in combination with various AI learning types (pre-training, transfer learning, reinforcement learning, active learning, etc.) and input representations (1D SMILES, 2D graph, 3D shape, binding site, pharmacophore, etc.), to enable customized solutions for a given molecular design scenario. Besides the usual generation followed screening protocol, goal-directed molecule generation can also be conducted towards predefined goals, enhancing the efficiency of hit identification, lead finding, and lead optimization. We demonstrate the effectiveness of ID4Idea platform through case studies, showcasing customized solutions for different design tasks using various input information, such as binding pockets, pharmacophores, and compound representations. In addition, remaining challenges are discussed to unlock the full potential of AI models in drug discovery and pave the way for the development of novel therapeutics.

Ketone bodies promote epididymal white adipose expansion to alleviate liver steatosis in response to a ketogenic diet.

Liver can sense the nutrient status and send signals to other organs to regulate overall metabolic homoeostasis. Herein, we demonstrate that ketone bodies act as signals released from the liver that specifically determine the distribution of excess lipid in epididymal white adipose tissue (eWAT) when exposed to a ketogenic diet (KD). An acute KD can immediately result in excess lipid deposition in the liver. Subsequently, the liver sends the ketone body ß-hydroxybutyrate (BHB) to regulate white adipose expansion, including adipogenesis and lipogenesis, to alleviate hepatic lipid accumulation. When ketone bodies are depleted by deleting 3-hydroxy-3-methylglutaryl-CoA synthase 2 gene in the liver, the enhanced lipid deposition in eWAT but not in inguinal white adipose tissue is preferentially blocked, while lipid accumulation in liver is not alleviated. Mechanistically, ketone body BHB can significantly decrease lysine acetylation of peroxisome proliferator-activated receptor gamma in eWAT, causing enhanced activity of peroxisome proliferator-activated receptor gamma, the key adipogenic transcription factor. These observations suggest that the liver senses metabolic stress first and sends a corresponding signal, that is, ketone body BHB, to specifically promote eWAT expansion to adapt to metabolic challenges.

Downregulation of transcription 1 hinders the replication of Dabie bandavirus by promoting the expression of TLR7, TLR8, and TLR9 signaling pathway.

Severe fever with thrombocytopenia syndrome virus (SFTSV) is a bunyavirus that causes SFTS, with a case fatality rate of up to 30 %. The innate immune system plays a crucial role in the defense against SFTSV; however, the impact of viral propagation of STFSV on the innate immune system remains unclear. Although proteomics analysis revealed that the expression of the downregulator of transcription 1 (DR1) increased after SFTSV infection, the specific change trend and the functional role of DR1 during viral infection remain unelucidated. In this study, we demonstrate that DR1 was highly expressed in response to SFTSV infection in HEK 293T cells using qRT-PCR and Western blot analysis. Furthermore, viral replication significantly increased the expression of various TLRs, especially TLR9. Our data indicated that DR1 positively regulated the expression of TLRs in HEK 293T cells, DR1 overexpression highly increased the expression of numerous TLRs, whereas RNAi-mediated DR1 silencing decreased TLR expression. Additionally, the myeloid differentiation primary response gene 88 (MyD88)-dependent or TIR-domain-containing adaptor inducing interferon-ß (TRIF)-dependent signaling pathways were highly up- and downregulated by the overexpression and silencing of DR1, respectively. Finally, we report that DR1 stimulates the expression of TLR7, TLR8, and TLR9, thereby upregulating the TRIF-dependent and MyD88-dependent signaling pathways during the SFTSV infection, attenuating viral replication, and enhancing the production of type I interferon and various inflammatory factors, including IL-1ß, IL-6, and IL-8. These results imply that DR1 defends against SFTSV replication by inducing the expression of TLR7, TLR8, and TLR9. Collectively, our findings revealed a novel role and mechanism of DR1 in mediating antiviral responses and innate immunity.