A pathological joint-liver axis mediated by matrikine-activated CD4+ T cells.

The knee joint has long been considered a closed system. The pathological effects of joint diseases on distant organs have not been investigated. Herein, our clinical data showed that post-traumatic joint damage, combined with joint bleeding (hemarthrosis), exhibits a worse liver function compared with healthy control. With mouse model, hemarthrosis induces both cartilage degeneration and remote liver damage. Next, we found that hemarthrosis induces the upregulation in ratio and differentiation towards Th17 cells of CD4+ T cells in peripheral blood and spleen. Deletion of CD4+ T cells reverses hemarthrosis-induced liver damage. Degeneration of cartilage matrix induced by hemarthrosis upregulates serological type II collagen (COL II), which activates CD4+ T cells. Systemic application of a COL II antibody blocks the activation. Furthermore, bulk RNAseq and single-cell qPCR analysis revealed that the cartilage Akt pathway is inhibited by blood treatment. Intra-articular application of Akt activator blocks the cartilage degeneration and thus protects against the liver impairment in mouse and pig models. Taken together, our study revealed a pathological joint-liver axis mediated by matrikine-activated CD4+ T cells, which refreshes the organ-crosstalk axis and provides a new treatment target for hemarthrosis-related disease. Intra-articular bleeding induces cartilage degradation through down-reulation of cartilage Akt pathway. During this process, the soluble COL II released from the damaged cartilage can activate peripheral CD4+ T cells, differention into Th17 cells and secretion of IL-17, which consequently induces liver impairment. Intra-articular application of sc79 (inhibitor of Akt pathway) can prevent the cartilage damage as well as its peripheral influences.

Soil Geobacteraceae are the key predictors of neurotoxic methylmercury bioaccumulation in rice.

Contamination of rice by the potent neurotoxin methylmercury (MeHg) originates from microbe-mediated Hg methylation in soils. However, the high diversity of Hg methylating microorganisms in soils hinders the prediction of MeHg formation and challenges the mitigation of MeHg bioaccumulation via regulating soil microbiomes. Here we explored the roles of various cropland microbial communities in MeHg formation in the potentials leading to MeHg accumulation in rice and reveal that Geobacteraceae are the key predictors of MeHg bioaccumulation in paddy soil systems. We characterized Hg methylating microorganisms from 67 cropland ecosystems across 3,600 latitudinal kilometres. The simulations of a rice-paddy biogeochemical model show that MeHg accumulation in rice is 1.3-1.7-fold more sensitive to changes in the relative abundance of Geobacteraceae compared to Hg input, which is recognized as the primary parameter in controlling MeHg exposure. These findings open up a window to predict MeHg formation and accumulation in human food webs, enabling more efficient mitigation of risks to human health through regulations of key soil microbiomes.

One-step flow synthesis of size-controlled polymer nanogels in a fluorocarbon microfluidic chip.

Synthetic polymer nanoparticles (NPs) with biomimetic properties are ideally suited for different biomedical applications such as drug delivery and direct therapy. However, bulk synthetic approaches can suffer from poor reproducibility and scalability when precise size control or multi-step procedures are required. Herein, we report an integrated microfluidic chip for the synthesis of polymer NPs. The chip could sequentially perform homopolymer synthesis and subsequent crosslinking into NPs without intermediate purification. This was made possible by fabrication of the chip with a fluorinated elastomer and incorporation of two microfluidic mixers. The first was a long channel with passive mixing features for the aqueous RAFT synthesis of stimuli-responsive polymers in ambient conditions. The polymers were then directly fed into a hydrodynamic flow focusing (HFF) junction that rapidly mixed them with a crosslinker solution to produce NPs. Compared to microfluidic systems made of PDMS or glass, our chip had better compatibility and facile fabrication. The polymers were synthesized with high monomer conversion and the NP size was found to be influenced by the flow rate ratio between the crosslinker solution and polymer solution. This allowed for the size to be predictably controlled by careful adjustment of the fluid flow rates. The size of the NPs and their stimuli-responses were studied using DLS and SEM imaging. This microfluidic chip design can potentially streamline and provide some automation for the bottom-up synthesis of polymer NPs while offering on-demand size control.

Modified stochastic diffusion particle tracking model driven by skew Brownian motion: Analysis of sediment particle motion in turbulent flow under the effects of ejection and sweep.

Turbulent bursting events have been classified into outward interactions (Q1), ejections (Q2), inward interactions (Q3), and sweeps (Q4) in various studies. Ejections (Q2) and sweeps (Q4) have been identified as significant contributors to time consumption, momentum flux, and sediment flux. Additionally, research has shown that the distribution of these events varies nonuniformly at different bed elevations. Despite extensive investigations into the nonuniform distribution of turbulent bursting events, their impact on sediment transport has been rarely explored. In this work, we developed a modified stochastic diffusion particle tracking model (SD-PTM) driven by skew Brownian motion (SBM) using the stochastic Lagrangian approach to scrutinize sediment particle movement in turbulent flows. The model incorporates turbulent characteristics derived from a direct numerical simulation dataset, allowing for a comprehensive analysis of sediment particle dynamics. Moreover, the proposed model accounts for the nonuniform spatial distribution of ejection and sweep events, as well as the particle movement direction during these events. Numerical simulations of the model were conducted to trace sediment particle trajectories in the streamwise and vertical directions. The analysis of sediment transport involved calculating the variance of particle trajectories to examine anomalous diffusion. The model's performance was evaluated by comparing it with flow velocity and sediment concentration profiles obtained from measurements in previous studies. In conclusion, our study suggests that the motion of sediment particles in turbulent flow can be thoroughly investigated under extreme flow conditions using the modified SD-PTM driven by SBM.

Development and validation of a deep learning model for predicting postoperative survival of patients with gastric cancer.

BACKGROUND: Deep learning (DL), a specialized form of machine learning (ML), is valuable for forecasting survival in various diseases. Its clinical applicability in real-world patients with gastric cancer (GC) has yet to be extensively validated. METHODS: A combined cohort of 11,414 GC patients from the Surveillance, Epidemiology and End Results (SEER) database and 2,846 patients from a Chinese dataset were utilized. The internal validation of different algorithms, including DL model, traditional ML models, and American Joint Committee on Cancer (AJCC) stage model, was conducted by training and testing sets on the SEER database, followed by external validation on the Chinese dataset. The performance of the algorithms was assessed using the area under the receiver operating characteristic curve, decision curve, and calibration curve. RESULTS: DL model demonstrated superior performance in terms of the area under the curve (AUC) at 1, 3, and, 5 years post-surgery across both datasets, surpassing other ML models and AJCC stage model, with AUCs of 0.77, 0.80, and 0.82 in the SEER dataset and 0.77, 0.76, and 0.75 in the Chinese dataset, respectively. Furthermore, decision curve analysis revealed that the DL model yielded greater net gains at 3 years than other ML models and AJCC stage model, and calibration plots at 3 years indicated a favorable level of consistency between the ML and actual observations during external validation. CONCLUSIONS: DL-based model was established to accurately predict the survival rate of postoperative patients with GC.

Protect the oceans from Japan's radioisotope dumping.

•Dumping of Fukushima's radioactive wastewater raises marine food web concern.•Tritium seems to be the most problematic compound.•Long-lived radioisotopes Biomagnify up to 50,000 folds in marine fish species.•This threatens fragile deep-sea ecosystems requiring immediate action.•Empowered Routine monitoring is crucial to maintain planetary health.

Antibacterial Effect and Possible Mechanism of Sesamol against Foodborne Pathogens.

Food safety problems caused by foodborne pathogens have become a major public issue, and the search for efficient and safe bacteriostatic agents has gained attention. Sesamol (SE), a phenolic compound abundant in sesame oil, offers numerous health benefits and exhibits certain antibacterial properties. The purpose of this study was to evaluate the antibacterial effect and potential mechanisms of SE against representative foodborne pathogens, including Listeria monocytogenes, Staphylococcus aureus, Bacillus cereus, Escherichia coli, and Salmonella serovar Enteritidis. The results showed that SE significantly inhibited the growth of the five pathogenic bacteria in sterile saline and pasteurized milk by 2.16-4.16 log10 CFU/g within 48 h. The results of the minimum bactericidal concentration and time-kill assay showed that SE had a greater inhibitory effect on L. monocytogenes compared with other bacteria. Additionally, SE was found to alter the cell membranes' permeability in these bacteria, resulting in the release of intercellular proteins and DNA. A scanning electron microscopy analysis showed that exposure to SE resulted in significant changes in bacterial morphology, producing cell shrinkage and deformation. These findings suggest that SE could inhibit both Gram-negative and Gram-positive bacteria by interfering with the function and morphology of bacterial cells.

Effective On-Line Performance Modulation and Efficient Continuous Preparation of Ultra-Long Twisted and Coiled Polymer Artificial Muscles for Engineering Applications.

Artificial muscle is a kind of thread-like actuator that can produce contractile strain, generate force, and output mechanical work under external stimulations to imitate the functions and achieve the performances of biological muscles. It can be used to actuate various bionic soft robots and has broad application prospects. The electrically controlled twisted and coiled polymer (TCP) artificial muscles, with the advantages of high power density, large stroke and low driving voltage, while also being electrolyte free, are the most practical. However, the relationship between the muscle performances and its preparation parameters is not very clear yet, and the complete procedure of designing and preparing TCP muscles according to actual needs has not been established. Besides, current preparation approaches are very time-consuming and cannot make ultra-long TCP muscles. These problems greatly limit wide applications of TCP artificial muscles. In this study, we studied and built the relationship between the actuating performances of TCP muscles and their preparation parameters, so that suitable TCP muscles can be easily designed and prepared according to actual requirements. Moreover, an efficient preparation method integrating one-step annealing technique has been developed to realize on-line performance modulation and continuous fabrication of ultra-long TCP muscles. By graphically assembling long muscles on heat-resist films, we designed and produced a series of fancy soft robots (butterfly, flower, starfish), which can perform various bionic movements and complete specific tasks. This work has achieved efficient on-demand preparation and large-scale assembly of ultra-long TCP muscles, laying solid foundations for their engineering applications in soft robot field.

A hidden demethylation pathway removes mercury from rice plants and mitigates mercury flux to food chains.

Dietary exposure to methylmercury (MeHg) causes irreversible damage to human cognition and is mitigated by photolysis and microbial demethylation of MeHg. Rice (Oryza sativa L.) has been identified as a major dietary source of MeHg. However, it remains unknown what drives the process within plants for MeHg to make its way from soils to rice and the subsequent human dietary exposure to Hg. Here we report a hidden pathway of MeHg demethylation independent of light and microorganisms in rice plants. This natural pathway is driven by reactive oxygen species generated in vivo, rapidly transforming MeHg to inorganic Hg and then eliminating Hg from plants as gaseous Hg°. MeHg concentrations in rice grains would increase by 2.4- to 4.7-fold without this pathway, which equates to intelligence quotient losses of 0.01-0.51 points per newborn in major rice-consuming countries, corresponding to annual economic losses of US$30.7-84.2 billion globally. This discovered pathway effectively removes Hg from human food webs, playing an important role in exposure mitigation and global Hg cycling.

Identification of key miRNAs in unilateral mastication-induced disruption of cartilage homeostasis.

OBJECTIVE: The present study identified potentially pivotal miRNAs contributing to chondrogenic differentiation in temporomandibular joint suffering abnormal stress. MATERIALS AND METHODS: Sprague-Dawley rats were randomly divided into control and experimental unilateral mastication (EUM) group. Bone micro-structure parameters was detected by micro-CT, and FGF-1 and MMP-1 expression was examined by immunohistochemistry. Differentially expressed miRNAs of bilateral condyle cartilage were screened via miRNA microarray at 4- and 8-week EUM, then further verified using quantitative reverse-transcription PCR. Over-expression of five differentially expressed miRNAs in chondrocytes was triggered by transfecting miRNA mimics. The expression of MMP-13, Col-II, OPN, and Runx2 was verified by western blotting. RESULTS: Expressions of FGF-1 and MMP-1 in right condyles gradually increased from 2 to 6 weeks after EUM. A total of 20 differentially expressed miRNAs were regulated by EUM, which related to cell proliferation, invasion, and osteoblast differentiation pathways. The over-expression of miR-148a-3p and miR-1-3p led to down-regulation of Col-II, while MMP-13 and Runx2 were up-regulated by induction of hypotrophic differentiation or IL-1ß stimulation. These findings suggested that miR-148a-3p and miR-1-3p promote chondrogenic differentiation. CONCLUSIONS: Several pivotal miRNAs were found to be related to chondrogenic differentiation, which provides novel insight into pathogenic mechanisms of cartilage homeostasis.

Omnidirectional Monolithic Marker for Intra-Operative MR-Based Positional Sensing in Closed MRI.

We present a design of an inductively coupled radio frequency (ICRF) marker for magnetic resonance (MR)-based positional tracking, enabling the robust increase of tracking signal at all scanning orientations in quadrature-excited closed MR imaging (MRI). The marker employs three curved resonant circuits fully covering a cylindrical surface that encloses the signal source. Each resonant circuit is a planar spiral inductor with parallel plate capacitors fabricated monolithically on flexible printed circuit board (FPC) and bent to achieve the curved structure. Size of the constructed marker is Ø3-mm ×5 -mm with quality factor > 22, and its tracking performance was validated with 1.5 T MRI scanner. As result, the marker remains as a high positive contrast spot under 360° rotations in 3 axes. The marker can be accurately localized with a maximum error of 0.56 mm under a displacement of 56 mm from the isocenter, along with an inherent standard deviation of 0.1-mm. Accrediting to the high image contrast, the presented marker enables automatic and real-time tracking in 3D without dependency on its orientation with respect to the MRI scanner receive coil. In combination with its small form-factor, the presented marker would facilitate robust and wireless MR-based tracking for intervention and clinical diagnosis. This method targets applications that can involve rotational changes in all axes (X-Y-Z).

Fibrillarin promotes homologous recombination repair by facilitating the recruitment of recombinase RAD51 to DNA damage sites. / çº¤ç»´è›‹ç™½é€šè¿‡ä¿ƒè¿›é‡ç»„é ¶RAD51在DNA损伤位点的招募参与同源重组修复.

Eukaryotic organisms constantly face a wide range of internal and external factors that cause damage to their DNA. Failure to accurately and efficiently repair these DNA lesions can result in genomic instability and the development of tumors (Canela et al., 2017). Among the various forms of DNA damage, DNA double-strand breaks (DSBs) are particularly harmful. Two major pathways, non-homologous end joining (NHEJ) and homologous recombination (HR), are primarily responsible for repairing DSBs (Katsuki et al., 2020; Li and Yuan, 2021; Zhang and Gong, 2021; Xiang et al., 2023). NHEJ is an error-prone repair mechanism that simply joins the broken ends together (Blunt et al., 1995; Hartley et al., 1995). In contrast, HR is a precise repair process. It involves multiple proteins in eukaryotic cells, with the RAD51 recombinase being the key player, which is analogous to bacterial recombinase A (RecA) (Shinohara et al., 1992). The central event in HR is the formation of RAD51-single-stranded DNA (ssDNA) nucleoprotein filaments that facilitate homology search and DNA strand invasion, ultimately leading to the initiation of repair synthesis (Miné et al., 2007; Hilario et al., 2009; Ma et al., 2017).

The hidden risk of microplastic-associated pathogens in aquatic environments.

Increasing studies of plastisphere have raised public concern about microplastics (MPs) as vectors for pathogens, especially in aquatic environments. However, the extent to which pathogens affect human health through MPs remains unclear, as controversies persist regarding the distinct pathogen colonization on MPs as well as the transmission routes and infection probability of MP-associated pathogens from water to humans. In this review, we critically discuss whether and how pathogens approach humans via MPs, shedding light on the potential health risks involved. Drawing on cutting-edge multidisciplinary research, we show that some MPs may facilitate the growth and long-range transmission of specific pathogens in aquatic environments, ultimately increasing the risk of infection in humans. We identify MP- and pathogen-rich settings, such as wastewater treatment plants, aquaculture farms, and swimming pools, as possible sites for human exposure to MP-associated pathogens. This review emphasizes the need for further research and targeted interventions to better understand and mitigate the potential health risks associated with MP-mediated pathogen transmission.

[Research Progress of Post-Transplant Cyclophosphamide Combined with Antithymocyte Globulin in Preventing GVHD after Hematopoietic Stem Cell Transplantation --Review].

Graft-versus-host disease (GVHD) is one of the major complications after allogeneic hematopoietic stem cell transplantation (allo-HSCT), which seriously affects the prognosis of patients. At present, a new regimen of post-transplantation cyclophosphamide (PTCy) combined with antithymocyte globulin (ATG) has been used to prevent GVHD, indicating that PTCy combined with ATG may have a good effect on the prevention of GVHD in different types of transplantation. However, the mechanism of this regimen, its effect on immune reconstitution and viral reactivation still needs to be further studied. Therefore, this article briefly reviews the research progress of PTCy combined with ATG in preventing GVHD after HSCT.

Contrast-enhanced ultrasound guided core needle biopsy for soft tissue tumors: Accuracy and applicability.

OBJECTIVE: To evaluate the effectiveness of contrast-enhanced ultrasound (CEUS) guided core needle biopsy (CNB) in diagnosing soft tissue tumors (STTs) and to identify the conventional ultrasonography (US) features of STTs that are recommended for CEUS-guided CNB. MATERIALS AND METHODS: A retrospective study was conducted on 123 patients with surgically confirmed STTs. Before surgeries, all subjects underwent CNB under the guidance of US or CEUS. The histopathological results of surgical specimens were considered as the gold standards. A successful biopsy diagnosis was defined as the pathological subtypes obtained by biopsy consistent with the gold standard. The diagnostic yields were compared between the US and CEUS groups, and the diagnostic yields based on various conventional US features of STTs were also compared between the two groups. RESULTS: Sixty-seven cases underwent US-guided CNB and fifty-six cases underwent CEUS-guided CNB. The clinical, biopsy, and conventional US characteristics revealed no significant difference between the two groups. The diagnostic yield of the CEUS group was statistically higher than that of the US group (p = 0.011). In the CEUS group, more STTs with the anechoic areas were identified after CEUS examination (p = 0.031). Furthermore, the diagnostic yields based on the conventional US features of STTs, including deep fascia layer (p = 0.010), a maximum diameter ≥5 cm (p = 0.037), rough margin (p = 0.016), heterogeneous echotexture (p = 0.017), and absence of anechoic area (p = 0.013), were significantly different between the two groups, and the CEUS group exhibited higher diagnostic yields. CONCLUSION: CEUS-guided CNB was found to be an efficient method for STTs diagnosis. It is particularly recommended for STTs with the following conventional US features, including location in deep fascia layer, a maximum diameter ≥5 cm, rough margin, heterogeneous echotexture, or absence of anechoic area.

[Advances in in vitro and in vivo models for Listeria monocytogenes placental infection].

Listeria monocytogenes is recognized as a significant foodborne pathogen, capable of causing listeriosis in humans, which is a global public health concern. This pathogen is particularly dangerous for pregnant women, as it can lead to invasive listeriosis in fetuses and neonates, posing a significant threat to both maternal and fetal health. Therefore, establishing suitable in vitro and in vivo models for L. monocytogenes placenta infection, as well as analyzing and exploring the infection process and its pathogenic mechanism, are important approaches to prevent and control L. monocytogenes infection in mothers and infants. In this study, we reviewed the in vitro and in vivo placental models used for studying the infection of L. monocytogenes in maternal and infant, summarized and discussed the advantages and limitations of each model, and explored the potential of in vitro cell models and organoids for the study of L. monocytogenes infection. This paper aims to support the study of the infection pathway and pathogenesis of listeriosis and provide scientific references for the prevention and control of L. monocytogenes infection.

Salubrinal alleviates cartilage degradation in a rabbit temporomandibular joint osteoarthritis model.

OBJECTIVE: To investigate and explain the beneficial effects of local intra-articular injection of Salubrinal on temporomandibular joint osteoarthritis (TMJOA) using a rabbit model of anterior disc displacement (ADD). METHODS: Rabbits were divided and subjected to surgical ADD. Salubrinal was administered by intra-articular injection in the TMJ every other day for 2 and 4 weeks after operation. Histological examination and TUNEL staining were then performed. Immunohistochemistry, quantitative real-time PCR, and Western blot analysis were employed to evaluate the expression of endoplasmic reticulum (ER) stress-related markers, catabolic factors, extracellular matrix proteins, inflammatory factors, and nuclear factor-kappa B (NF-κB) activation. RESULTS: In the ADD groups, we found that Salubrinal partly reversed condylar cartilage deterioration according to the histological analysis. Salubrinal reduced chondrocytes apoptosis while increased matrix components including Collagen II and Aggrecan. Meanwhile, Salubrinal downregulated the catabolic expression of MMP13, ADAMTS5, VEGF, TNF-α, and IL-1ß. We also observed that Salubrinal inhibited ER stress activation by reducing the expression of GRP78, CHOP, ATF4, and Caspase-12. Additionally, Salubrinal suppressed the phosphorylation of NF-κB. CONCLUSION: These results indicate that Salubrinal alleviates cartilage degradation following ADD, suggesting that intra-articular injection of Salubrinal is a potential therapeutic approach for preventing TMJOA.

Secure semantic optical communication scheme based on the multi-head attention mechanism.

In this paper, an artificial-intelligence-based secure semantic optical communication scheme is proposed. The semantic features of the original text information are extracted using Transformer. Compared with other networks, Transformer reduces the complexity of the structure and the associated training cost by using the multi-head attention mechanism. To solve the security problem, the encryption scheme is applied to an orthogonal frequency division multiplexed passive optical network (OFDM-PON). The proposed scheme applies chaotic sequences to produce masking vectors. We encrypt the constellation and frequency, achieving a large key space of 1 × 10270. To prove that Transformer can effectively extract the semantic features of text, we have computed the values of ROUGE-1, ROUGE-2, and ROUGE-L, which are 40.9, 18.02, and 37.17, respectively. An encrypted 16 quadrature amplitude modulation (16QAM) OFDM signal transmission over a 2 km seven-core fiber with a data rate of 78.5 Gbits/s was experimentally demonstrated. During the experiments, the bit error rate (BER) was analyzed and the results show that the proposed system improves efficiency and security in an OFDM-PON system.

Record-High Ultrasound-Sensitive NO Nanogenerators for Cascade Tumor Pyroptosis and Immunotherapy.

Pyroptosis is a pro-inflammatory cell death that is associated with innate immunity promotion against tumors. Excess nitric oxide (NO)-triggered nitric stress has potential to induce pyroptosis, but the precise delivery of NO is challenging. Ultrasound (US)-responsive NO production has dominant priority due to its deep penetration, low side effects, noninvasion, and local activation manner. In this work, US-sensitive NO donor N-methyl-N-nitrosoaniline (NMA) with thermodynamically favorable structure is selected and loaded into hyaluronic acid (HA)-modified hollow manganese dioxide nanoparticles (hMnO2 NPs) to fabricate hMnO2 @HA@NMA (MHN) nanogenerators (NGs). The obtained NGs have a record-high NO generation efficiency under US irradiation and can release Mn2+ after targeting the tumor sites. Later on, cascade tumor pyroptosis and cyclic GMP-AMP synthase-stimulator of interferon genes (cGAS-STING)-based immunotherapy is achieved and tumor growth is effectively inhibited.

VGAEDTI: drug-target interaction prediction based on variational inference and graph autoencoder.

MOTIVATION: Accurate identification of Drug-Target Interactions (DTIs) plays a crucial role in many stages of drug development and drug repurposing. (i) Traditional methods do not consider the use of multi-source data and do not consider the complex relationship between data sources. (ii) How to better mine the hidden features of drug and target space from high-dimensional data, and better solve the accuracy and robustness of the model. RESULTS: To solve the above problems, a novel prediction model named VGAEDTI is proposed in this paper. We constructed a heterogeneous network with multiple sources of information using multiple types of drug and target dataIn order to obtain deeper features of drugs and targets, we use two different autoencoders. One is variational graph autoencoder (VGAE) which is used to infer feature representations from drug and target spaces. The second is graph autoencoder (GAE) propagating labels between known DTIs. Experimental results on two public datasets show that the prediction accuracy of VGAEDTI is better than that of six DTIs prediction methods. These results indicate that model can predict new DTIs and provide an effective tool for accelerating drug development and repurposing.