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Within the realm of mixed reality, the capability to dynamically render environmental effects with high realism plays a crucial role in amplifying user engagement and interaction. Fluid dynamics, in particular, stand out as essential elements for crafting immersive virtual settings. This includes the simulation of phenomena like smoke, fire, and clouds, which are instrumental in enriching the virtual experience. This work showcases a cutting-edge system developed to produce dynamic and interactive fluid effects that mirror real captured data in real-time for mixed reality applications. This innovative system seamlessly incorporates fluid reconstruction alongside velocity estimation processes within the Unity engine environment. Our approach leverages a novel physics-based differentiable rendering technique, grounded in the principles of light transport in participating media, to simulate the intricate behaviors of fluid while ensuring high fidelity in visual appearance. To further enhance realism, we have expanded our framework to include the estimation of velocity fields, addressing the critical need for fluid motion simulation. The practical application of these techniques demonstrates the system's capacity to offer a robust platform for fluid modeling in mixed reality environments. Through extensive evaluations, we illustrate the effectiveness of our approach in various scenes, underscoring its potential to transform mixed reality content creation by providing developers with the tools to incorporate highly realistic and interactive fluid seamlessly.

Regulatory T (Treg) cells play a central role in immune homeostasis. Forkhead box P3 (Foxp3), a hallmark molecule in Treg cells, is a vital transcription factor for their development and function. Studies have shown that degradation of the Foxp3 could provide therapeutic benefits in achieving effective anti-tumor immunity. In this study, we designed three PROTAC molecules, P60-L1-VHL, P60-L2-VHL, and P60-L3-VHL, based on a 15-mer peptide inhibitor of Foxp3 (P60), and explored their potential in regulating Foxp3 expression and function. Our data show that, among these molecules, P60-L3-VHL can inhibit the expression and nuclear localization of Foxp3 in HEK 293 T and HeLa cells, respectively. Meanwhile, use of proteasome inhibitor in P60-L3-VHL treated cells revealed an increased Foxp3 expression, indicating that P60-L3-VHL mediates the inhibition of Foxp3 through its degradation in the proteasome pathway. We further substantiate that P60-L3-VHL reduces the differentiation and Foxp3 expression in the in-vitro activated Treg cells. Overall, our findings suggest that P60-L3-VHL inhibits the differentiation of Treg cells by degrading the Foxp3, which may have potential implications in cancer immunotherapy., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

The purpose of the study was to examine whether magnesium (Mg) depletion score (MDS) and dietary Mg intake are associated in adults with the risk of developing Parkinson's disease (PD). In this study, we analyzed data from the National Health and Nutrition Examination Survey (NHANES), which included 20,010 adults aged over 40 years old. To evaluate the linear association between PD and dietary intake of Mg or MDS, we conducted weighted logistic regression for univariate analysis and multivariate linear regression models. Odds ratios (OR) and 95% confidence intervals (CI) were estimated using logistic regression models. A restricted cubic spline (RCS) was drawn to visualize the nonlinear relationship between MDS/dietary Mg intake and PD. In addition, we examined the variations in the relationship between MDS and PD across different confounding factors of the association using subgroup analysis. There were 240 PD cases (1.2%), and 19770 non-PD were included in the study. We found that a higher MDS was associated with an increased risk of PD after adjusting for covariates (OR per 1-unit increase, 1.47; 95% CI, 1.16-1.86). There is insufficient evidence to support a significant statistical association between Mg intake and the risk of PD. According to nonlinear regression, high MDS was associated with higher odds of PD and lower odds of PD above 250 mg/day intake of Mg. It has been shown that Mg bioavailability may be negatively associated with PD as measured by MDS. MDS is a potential method for screening the population with PD. Maintaining adequate Mg status may be important for PD prevention., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

CRISPR/Cas12a system, renowned for its precise recognition and efficient nucleic acid cleavage capabilities, has demonstrated remarkable performance in molecular diagnostics and biosensing. However, the reported Cas12a activity regulation methods often involved intricate CRISPR RNA (crRNA) structural adjustments or costly chemical modifications, which limited their applications. Here, we demonstrated a unique enzyme activity engineering strategy using flap endonuclease 1 (FEN1) to regulate the accessibility of the protospacer adjacent motif (PAM) module in the double-stranded DNA activator (FRAME). By identifying the three-base overlapping structure between the target inputs and substrate, FEN1 selectively cleaved and released the 5'-flap containing the 'TTTN' sequence, which triggered the secondary cleavage of FEN1 while forming a nicked PAM, ultimately achieving the sensitive switching of Cas12a's activity. The FRAME strategy exemplified the 'two birds with one stone' principle, as it not only precisely programmed Cas12a's activity but also simultaneously triggered isothermal cyclic amplification. Moreover, the FRAME strategy was applied to construct a sensing platform for detecting myeloperoxidase and miR-155, which demonstrated high sensitivity and specificity. Importantly, it proved its versatility in detecting multiple targets using a single crRNA without redesign. Collectively, the FRAME strategy opens up a novel avenue for modulating Cas12a's activity, promising immense potential in the realm of medical diagnostics., (© The Author(s) 2024. Published by Oxford University Press on behalf of Nucleic Acids Research.)

Osteoarthritis and sports injuries often lead to cartilage defects. How to promote its repair and rebuild the smooth cartilage surface has been a hot spot of research in recent years. Kartogenin (KGN), a small molecule discovered in recent years, has been shown to promote the proliferation and chondrogenic differentiation of mesenchymal stem cells (MSCs). As more and more studies have been conducted on KGN, its mechanism of action has been gradually revealed. However, KGN is insoluble in water and therefore easily removed by body fluids. In order to address such issues, a number of systems for efficient intra-articular delivery of KGN have been developed. In addition, due to the complex pathology of cartilage repair, KGN is often used in combination with other drugs to target different stages. In addition, with the rapid development of tissue engineering, scholars have combined KGN with various scaffolds by physical or chemical methods. In this paper, we firstly introduce the general properties of KGN followed by a review of the latest advances in the intra-articular delivery modes of KGN. Finally, we discuss the prospects for the application of KGN in cartilage regeneration, which is aimed at providing a new idea and target for the treatment of cartilage defects., Competing Interests: The author declares no conflict of interest, financial or otherwise., (This journal is © The Royal Society of Chemistry.)

Background: Androgen deprivation therapy (ADT) resistance is closely associated with altered AR status. Aberrant AR expression is critical for the induction of ADT resistance, necessitating the identification of an anti-PCa target independent of AR expression., Methods: Transcriptomic data and clinical information of PRAD were obtained from TCGA database. Genes with PCa-related and AR expression-independent were screened by bioinformatics, and characterized by PPI and GO functional enrichment analyses. Candidate genes were locked by co-expression correlation and disease-free survival (DFS) analyses. A prognostic gene set was established using LASSO Cox regression algorithm. Cox proportional risk regression was performed to identify a key prognostic gene. Expression of the target protein in PCa tissues was verified by The Human Protein Atlas database. In vitro validation of cellular function and molecular mechanism by knockdown and overexpression of the target gene., Results: Two AR expression-independent genes (SLC43A1 and XRCC3) were available for the optimal prognostic model. This gene set effectively predicted PRAD patients' DFS at 1-, 3- and 5-year, where XRCC3 and tumor (T) stage were independent risk factors. XRCC3 was higher expressed in PRAD patients with T3-T4 stages and accompanied by poorer DFS. IHC staining also validated its higher expression in high-risk PCa tissues. In vitro experiments demonstrated that silencing XRCC3 significantly inhibited 22Rv1 and DU145 cell proliferation, migration and invasion, while promoted apoptosis. Further, silencing XRCC3 promoted DNA damage-induced p53/Bax signaling pathway activation, which was absent with overexpression., Conclusion: Silencing XRCC3 exerts anti-PCa effects by promoting DNA damage-induced p53/Bax signaling pathway activation in an AR expression-independent manner., (© 2024. The Author(s).)

The development of efficient and durable electrocatalysts for the alkaline hydrogen oxidation/evolution reaction is crucial for anion exchange membrane fuel cells/water electrolyzers. However, designing such electrocatalysts poses a challenge due to the need for optimizing various adsorbates. Herein, highly dispersed Ru nanoparticles catalysts is reported encapsulated and supported by defective anatase phase of titanium dioxide (named as Ru NPs/def-TiO 2 (A)) for boosting hydrogen-cycle electrocatalysis with robust anti-CO-poisoning in alkaline conditions. The Ru NPs/def-TiO 2 (A) achieves a high-quality activity of 7.65 A mg Ru -1 , which is 23.2 and 9.5-fold higher than commercial Ru/C and Pt/C in alkaline HOR. Moreover, this catalyst exhibits an outstanding overpotential of 21 mV at 10 mA cm -2 in alkaline HER. Hydrogen underpotential deposition (H upd ) and CO stripping experiments demonstrate that Ru NPs/def-TiO 2 (A) has the optimized H*, OH*, and CO* adsorption strength, enabling the Ru NPs/def-TiO 2 (A) catalyst to display excellent and robust HOR/HER performance under alkaline conditions. Using density functional theory calculations, the enhanced HOR performance mechanism for the Ru NPs/def-TiO 2 (A) catalyst originates from the TiO 2 step face in contact with the Ru nanoparticles, indicating that the kinetics of water formation are considerably more favorable at the Ru NPs/def-TiO 2 (A) interface., (© 2024 Wiley‐VCH GmbH.)

Infection with pathogens can increase the fecundity and other fitness-related traits of insect vectors for their own advantage. Our previous research has reported the pivotal role of DcKr-h1 in the fecundity improvement of Diaphorina citri induced by the bacterium, " Candidatus Liberibacter asiaticus" ( C Las), and the fungus, Cordyceps fumosorosea ( Cf ). However, the posttranscriptional regulation of this process remains poorly understood. Given the significance of miRNAs in gene regulation, we delved into their roles in shaping phenotypes and their underlying molecular mechanisms. Our results indicated that two miRNAs, miR-2 and novel-miR-109, jointly inhibited DcKr-h1 expression by binding to its 3' untranslated region (UTR). In the D. citri-C Las interaction, the expression levels of miR-2 and novel-miR-109 in the ovaries of C Las-positive psyllids were lower compared to C Las-negative individuals. Overexpression of miR-2 or novel-miR-109 significantly decreased fecundity and C Las titer in ovaries and caused reproductive defects reminiscent of DcKr-h1 knockdown. Similarly, in the D. citri-Cf interaction, the levels of miR-2 and novel-miR-109 markedly decreased in the ovaries. Upregulation of miR-2 or novel-miR-109 also resulted in reduced fecundity and ovary defects similar to those caused by DcKr-h1 silencing. Moreover, feeding antagomir-2 or antagomir-109 partially rescued the defective phenotypes caused by DcKr-h1 silencing in both model systems, and miR-2 and novel-miR-109 were repressed by juvenile hormone (JH) and regulated the genes associated with egg development. This study shows a conserved regulatory mechanism, whereby JH suppresses the expression of miR-2 and novel-miR-109 which, together with JH-induced transcription of DcKr-h1 , increases female fecundity induced by both symbiotic bacteria and pathogenic fungi., Importance: Infection with pathogens can increase the fecundity and other fitness-related traits of insect vectors for their own advantage. Our previous research has reported that DcKr-h1 plays a critical role in the increase in fecundity of Diaphorina citri induced by the bacterium, "Candidatus Liberibacter asiaticus" ( C Las) and the fungus, Cordyceps fumosorosea ( Cf ). However, the posttranscriptional regulation of this process remains poorly understood. Given the significance of miRNAs in gene regulation, we delved into their roles in shaping phenotypes and their underlying molecular mechanisms. Our results indicated that two miRNAs, miR-2 and novel-miR-109, jointly inhibited DcKr-h1 expression by binding to its 3' untranslated region (UTR). In both D. citri - C Las and D. citri - Cf interactions, the increased juvenile hormone (JH) titer and reduced abundance of miR-2 and novel-miR-109 ensure high levels of DcKr-h1 expression, consequently stimulating ovarian development and enhancing fecundity. These observations provide evidence that miR-2 and miR-109 are crucial players in the JH-dependent increase in fecundity in psyllids induced by infection with different pathogens.

Pulse wave analysis, a non-invasive and cuff-less approach, holds promise for blood pressure (BP) measurement in precision medicine. In recent years, pulse wave learning for BP estimation has undergone extensive scrutiny. However, prevailing methods still encounter challenges in grasping comprehensive features from pulse waves and generalizing these insights for precise BP estimation. In this study, we propose a general pulse wave deep learning (PWDL) approach for BP estimation, introduc-ing the OVAR-BPnet model to powerfully capture intricate pulse wave features and showcasing its effectiveness on multiple types of pulse waves. The approach involves constructing population pulse waves and employing a model comprising an omni-scale convolution subnet, a Vision Transformer subnet, and a multilayer perceptron subnet. This design enables the learning of both single-period and multi-period waveform features from multiple subjects. Additionally, the approach employs a data augmentation strategy to enhance the morphological features of pulse waves and devise a label sequence regularization strategy to strengthen the intrinsic relationship of the subnets' output. Notably, this is the first study to validate the performance of the deep learning approach of BP estimation on three types of pulse waves: photoplethysmography, forehead imaging photoplethysmography, and radial artery pulse pressure waveform. Experiments show that the OVAR-BPnet model has achieved advanced levels in both evaluation indicators and international evaluation criteria, demonstrating its excellent competitiveness and generalizability. The PWDL approach has the potential for widespread application in convenient and continuous BP monitoring systems.

Cryptocaryon irritans, a protozoan parasite that infects marine fish, is characterized by a complex life cycle that includes a cyst-forming reproductive phase. However, the composition of the cyst wall and mechanism of its formation remain unclear. In this study, we identified chitin as a key component of the cyst wall using calcofluor white and wheat germ agglutinin, with Fourier-transform infrared spectroscopy confirming its β-form structure. Two chitin synthase genes, CHS1 and CHS2, were identified as being expressed throughout the life cycle and show close phylogenetic relationships with chitin synthase from ciliates. Incubation with specific anti-CHS1 and -CHS2 antibodies significantly reduced both the thickness and chitin content of the cyst wall, highlighting the critical role of these enzymes in chitin biosynthesis. Treatment with benzoylureas, which inhibit chitin synthesis, caused thinning of the cyst wall and downregulation of CHS gene expression, resulting in an 84 % reduction in the hatching rate after treatment with 0.01 mM CuSO 4 compared with control tomonts. Western blot analysis demonstrated that recombinant CHS proteins are immunogenic, and tomonts from CHS-immunized grouper exhibited reduced size. These findings bridge a crucial knowledge gap in understanding of the C. irritans cyst wall and highlight promising targets for infection prevention and control strategies., Competing Interests: Declaration of competing interest We declare that we have no financial and personal relationships with other people or organizations that can inappropriately influence our work, there is no professional or other personal interest of any nature or kind in any product, service and/or company that could be construed as influencing the position presented in, or the review of, the manuscript entitled., (Copyright © 2024. Published by Elsevier B.V.)

The Sir2 enzyme from Plasmodium falciparum ( Pf Sir2A) is essential for the antigenic variation of this parasite, and its inhibition is expected to have therapeutic effects for malaria. Selective Pf Sir2A inhibitors are not available yet, partially due to the fact that this enzyme demonstrates extremely weak in vitro deacetylase activity, making the characterization of its inhibitors rather challenging. In the current study, we report the biochemical characterization and inhibitor discovery for this enzyme. Pf Sir2A exhibits greater enzymatic activity in the presence of DNA for both the peptide and histone protein substrates, suggesting that nucleosomes may be the real substrates of this enzyme. Indeed, it demonstrates robust deacetylase activity against nucleosome substrates, stemming primarily from the tight binding interactions with the nucleosome. In addition to DNA/nucleosome, free fatty acids (FFAs) are also identified as endogenous Pf Sir2A regulators. Myristic acid, a biologically relevant FFA, shows differential regulation of the two distinct activities of Pf Sir2A: activates deacetylation, but inhibits defatty-acylation. The structural basis of this differential regulation was further explored. Moreover, synthetic small molecule inhibitors of Pf Sir2A were discovered through the screening of a library of human sirtuin regulators. The mechanism of inhibition of the lead compounds were investigated. Collectively, the mechanistic insights and inhibitors described in this study will facilitate the future development of small molecule Pf Sir2A inhibitors as antimalarial agents.

The accurate extraction of buildings from remote sensing images is crucial in fields such as 3D urban planning, disaster detection, and military reconnaissance. In recent years, models based on Transformer have performed well in global information processing and contextual relationship modeling, but suffer from high computational costs and insufficient ability to capture local information. In contrast, convolutional neural networks (CNNs) are very effective in extracting local features, but have a limited ability to process global information. In this paper, an asymmetric network (CTANet), which combines the advantages of CNN and Transformer, is proposed to achieve efficient extraction of buildings. Specifically, CTANet employs ConvNeXt as an encoder to extract features and combines it with an efficient bilateral hybrid attention transformer (BHAFormer) which is designed as a decoder. The BHAFormer establishes global dependencies from both texture edge features and background information perspectives to extract buildings more accurately while maintaining a low computational cost. Additionally, the multiscale mixed attention mechanism module (MSM-AMM) is introduced to learn the multiscale semantic information and channel representations of the encoder features to reduce noise interference and compensate for the loss of information in the downsampling process. Experimental results show that the proposed model achieves the best F1-score (86.7%, 95.74%, and 90.52%) and IoU (76.52%, 91.84%, and 82.68%) compared to other state-of-the-art methods on the Massachusetts building dataset, the WHU building dataset, and the Inria aerial image labeling dataset.

The microplastics (MPs), a novel pollutant, and heavy metals (HMs) significantly affect soil ecology. The study investigated HMs and MPs in Qianxi's high geological background soil, established a model for risk evaluation with MPs types and shapes, and proposed a two-dimensional comprehensive index model for MPs-HMs combined pollution and risk evaluation criterion. The results revealed a high soil Cd concentration, with a mean value of 0.38 mg·kg -1 . Additionally, soils from soybean-wheat intercropping-potato-corn rotation (SWI-PCR) exhibited significantly higher concentrations of Hg, As, and Pb compared with those from soybean-wheat intercropping-corn rotation (SWI-CR). Moreover, the soil exhibited a high abundance of MPs (8667.66 ± 3864.26 items·kg -1 ), mainly characterized by PS and fiber. The mean of adjusted ecological risk index (ARI) for MPs in soil was 525.27, indicating a grade 3 risk. The two-dimensional combined index (TPI) was used to assess the ecological risk of MPs-HMs combined pollution, exhibiting an exceedance rate of 56 % with a mean of 445.07. The risk level of the combined pollution was graded as 6, indicating high risk. The microplastic risk evaluation model and the comprehensive evaluation method of combined pollution established in this study provide a reference for the future risk evaluation of multi-pollutant combined pollution., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

This study aimed to gather the best evidence on the relationship between dietary factors and hyperuricaemia and gout. We searched databases including PubMed, Embase, Cochrane, and Web of Science from database creation to July 2023. Meta-analysis showed that consumption of alcohol (OR: 1.41, 95% CI: 1.29-1.55; 1.60, 95% CI: 1.33-1.93, respectively), red meat (OR:1.27, 95% CI: 1.18-1.37; 1.32, 95% CI: 1.18-1.47, respectively), fructose (OR: 1.29, 95% CI: 1.21-1.38; 1.65, 95% CI: 1.36-2.01, respectively) and seafoods (OR: 1.40, 95% CI: 1.20-1.64; 1.29, 95% CI: 1.00-1.67, respectively) were positively associated with the risk of hyperuricaemia and gout, while vegetables (OR: 0.78, 95% CI: 0.71-0.85; 0.96,95% CI 0.74-1.24, respectively) were inversely associated. Dairy products (OR: 0.69, 95% CI: 0.61-0.78) and nuts (OR: 0.75, 95% CI: 0.60-0.93) were also inversely associated with the risk of hyperuricaemia. Soy products (OR: 0.86, 95% CI: 0.75-0.98) and coffee (OR: 0.56, 95% CI: 0.39-0.81) were negatively associated with the risk of gout.

Type D trichothecene toxins represent a class of macrocyclic trichothecene toxins with significant cytotoxicities towards human and crops. These toxins can also be used as anti-tumor compounds by the combination of antibody-drug conjugate. Therefore, it is urgent to investigate the biosynthetic routine of type D trichothecene toxins and explore type D trichothecene toxin-resistant genes, in order to ameliorate the hazard of trichothecene toxins and to facilitate the heterologous expression of toxin-biosynthetic cluster. In this study, tri18 gene was firstly knocked out in Paramyrothecium roridum, leading to the complete absence of type D trichothecene toxin epiroridin E, which can be restored by the complement of tri18 gene. Additionally, the knockout of tri18 gene led to a significant reduction in the pathogenicity of P. roridum towards pumpkin. Meanwhile, the enzymatic properties of Tri18 protein towards trichothecene deoxynivalenol (DON) toxin were also characterized. Moreover, tri3 and tri17KR with broad spectrum toxin-resistance function within the tri cluster were initially discovered through heterologous expression in toxin-sensitive Saccharomyces cerevisiae. And this study provides innovative type D trichothecene toxin resistant enzymes, which can provides green platform for the production of type D trichothecene toxins, thus promoting the application of these toxins in biomedical field., Competing Interests: Declaration of competing interest All the authors declare no conflict of interest for this article., (Copyright © 2024. Published by Elsevier B.V.)

Diabetic wound (DW), notorious for prolonged healing processes due to the unregulated immune response, neuropathy, and persistent infection, poses a significant challenge to clinical management. Current strategies for treating DW primarily focus on alleviating the inflammatory milieu or promoting angiogenesis, while limited attention has been given to modulating the neuro-immune microenvironment. Thus, we present an electrically conductive hydrogel dressing and identify its neurogenesis influence in a nerve injury animal model initially by encouraging the proliferation and migration of Schwann cells. Further, endowed with the synergizing effect of near-infrared responsive release of curcumin and nature-inspired artificial heterogeneous melanin nanoparticles, it can harmonize the immune microenvironment by restoring the macrophage phenotype and scavenging excessive reactive oxygen species. This in-situ formed hydrogel also exhibits mild photothermal therapy antibacterial efficacy. In the infected DW model, this hydrogel effectively supports nerve regeneration and mitigates the immune microenvironment, thereby expediting the healing progress. The versatile hydrogel exhibits significant therapeutic potential for application in DW healing through fine-tuning the neuro-immune microenvironment., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Iron oxide @ biochar (FeO/C) promotes bacterial growth and facilitates electron transfer, thereby effectively promoting malathion degradation by Shewanella oneidensis MR-1 (S. oneidensis MR-1). This study elucidated the underlying mechanism of FeO/C-enhanced malathion degradation by S. oneidensis MR-1 through a combination of metabolomics and proteomics analysis. The kinetic fitting results from the degradation experiment indicated that 0.1 g/L FeO/C exerted the most significant enhancement effect on malathion degradation by S. oneidensis MR-1. Observations from Scanning Electron Microscopy and Laser Scanning Confocal Microscopy, along with physiological and biochemical analysis, showed that FeO/C enhanced the growth and oxidative response of S. oneidensis MR-1 under malathion stress. In addition, metabolomics and proteomics analysis revealed an increase in certain electron transfer related metabolites, such as coenzymes, and the upregulation of proteins, including coenzyme A, sdhD, and petC. Overall, spectroscopic analysis suggested that Fe 2+ , which was reduced from Fe 3+ by S. oneidensis MR-1 in FeO/C, promoted electron transfer in S. oneidensis MR-1 to enhance the degradation of malathion. This study offers enhanced strategies for efficient removal of malathion contaminants., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

The immunosuppressive phenotype of tumor cells extensively attenuates the immune activation effects of traditional treatments. In this work, a transferrin receptor (TfR) targeted immunostimulant (PTI) is fabricated for photodynamic immunotherapy against metastatic tumors by interrupting β -catenin signal pathway. To synthesize PTI, the photosensitizer conjugated TfR targeting peptide moiety (Palmitic-K(PpIX)-HAIYPRH) is unitized to encapsulate the transcription interrupter of ICG-001. On the one hand, the recognition of PTI and TfR can promote drug delivery into tumor cells to destruct primary tumors through photodynamic therapy and initiate an immunogenic cell death with the release of tumor-associated antigens. On the other hand, PTI will interrupt the binding between β -catenin and cAMP response element-binding protein (CREB), regulating the gene transcription to downregulate programmed death ligand 1 (PD-L1) while upregulating C-C motif chemokine ligand 4 (CCL4). Furthermore, the elevated CCL4 can recruit the dendritic cells to present tumor-specific antigens and promote T cells activation and infiltration, and the downregulated PD-L1 can avoid the immune evasion of tumor cells and activate systemic anti-tumor immunity to eradicate lung metastasis. This work may inspire the development of antibody antibody-free strategy to activate systemic immune response in consideration of immunosuppressive conditions., Competing Interests: The authors have no conflicts of interest to declare., (© 2024 The Authors.)

Background and Objective: Recent studies have highlighted the key role of the ATP-binding cassette (ABC) transporters, including the P-glycoprotein (P-gp), the breast cancer resistance protein (BCRP), and the multi-drug resistance protein 4 (MRP4) in limiting the brain distribution of several antiviral agents. In this study, we investigated whether the inhibition of these transporters increases the permeability of the blood-brain barrier (BBB) to ganciclovir., Methods: A microdialysis and high-performance liquid chromatographic method was developed to monitor the concentrations of unbound ganciclovir in the brain interstitial fluid and plasma, with and without the administration of ABC transporter inhibitors. Pharmacokinetic parameters, including the area under the plasma concentration-time curve from time 0 to time of the last measurable analyte concentration (AUC 0-t,plasma ), the area under the brain interstitial fluid concentration-time curve from time 0 to time of the last measurable analyte concentration (AUC 0-t,brain ), and the unbound brain-to-plasma concentration ratio (K p,uu,brain ) were calculated., Results: The mean AUC 0-t,plasma , AUC 0-t,brain , and K p,uu,brain in rats who received ganciclovir (30 mg/kg, intraperitoneal) alone were 1090 min·µg/mL, 150 min·µg/mL, and 14%, respectively. After the administration of tariquidar (inhibitor of P-gp), Ko143 (inhibitor of BCRP), or MK-571 (inhibitor of MRP4), the K p,uu,brain of ganciclovir increased to 31 ± 2.1%, 26 ± 1.3%, and 32 ± 2.0%, respectively., Conclusions: The findings of this study suggest that ABC transporters P-gp, BCRP, and MRP4 mediate the efflux of ganciclovir at the BBB and that the inhibition of these transporters facilitates the penetration of the BBB by ganciclovir., (© 2024. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Background: Prior studies have reported inconsistent results regarding the association between driving pressure-guided ventilation and postoperative pulmonary complications (PPCs). We aimed to investigate whether driving pressure-guided ventilation is associated with a lower risk of PPCs., Methods: We systematically searched electronic databases for RCTs comparing driving pressure-guided ventilation with conventional protective ventilation in adult surgical patients. The primary outcome was a composite of PPCs. Secondary outcomes were pneumonia, atelectasis, and acute respiratory distress syndrome (ARDS). Meta-analysis and subgroup analysis were conducted to calculate risk ratios (RRs) with 95% confidence intervals (CI). Trial sequential analysis (TSA) was used to assess the conclusiveness of evidence., Results: Thirteen RCTs with 3401 subjects were included. Driving pressure-guided ventilation was associated with a lower risk of PPCs (RR 0.70, 95% CI 0.56-0.87, P=0.001), as indicated by TSA. Subgroup analysis (P for interaction=0.04) found that the association was observed in non-cardiothoracic surgery (nine RCTs, 1038 subjects, RR 0.61, 95% CI 0.48-0.77, P< 0.0001), with TSA suggesting sufficient evidence and conclusive result; however, it did not reach significance in cardiothoracic surgery (four RCTs, 2363 subjects, RR 0.86, 95% CI 0.67-1.10, P=0.23), with TSA indicating insufficient evidence and inconclusive result. Similarly, a lower risk of pneumonia was found in non-cardiothoracic surgery but not in cardiothoracic surgery (P for interaction=0.046). No significant differences were found in atelectasis and ARDS between the two ventilation strategies., Conclusions: Driving pressure-guided ventilation was associated with a lower risk of postoperative pulmonary complications in non-cardiothoracic surgery but not in cardiothoracic surgery., Systematic Review Protocol: INPLASY 202410068., (Copyright © 2024 British Journal of Anaesthesia. Published by Elsevier Ltd. All rights reserved.)

Objective: To explore the complex mechanisms of keloid, new approaches have been developed by different strategies. However, conventional treatment did not significantly reduce the recurrence rate. This study aimed to identify new biomarkers and mechanisms for keloid progression through bioinformatics analyses., Methods: In our study, microarray datasets for keloid were downloaded from the GEO database. Differentially expressed genes (DEGs) were identified by R software. Multiple bioinformatics tools were used to identify hub genes, and reverse predict upstream miRNAs and lncRNA molecules of target hub genes. Finally, the total RNA-sequencing technique and miRNA microarray were combined to validate the identified genes., Results: Thirty-one DEGs were screened out and the upregulated hub gene SPP1 was finally identified, which was consistent with our RNA-sequencing analysis results and validation dataset. In addition, a ceRNA network of mRNA (SPP1)-miRNA (miR-181a-5p)-lncRNA (NEAT1, MALAT1, LINC00667, NORAD, XIST and MIR4458HG) was identified by the bioinformatics databases. The results of our miRNA microarray showed that miR-181a-5p was upregulated in keloid, also we found that the lncRNA NEAT1 could affect keloid progression by retrieving the relevant literature., Conclusions: We speculate that SPP1 is a potential candidate biomarker and therapeutic target for patients with keloid, and NEAT1/miR-181a-5p/SPP1 might be the RNA regulatory pathway that regulates keloid formation.

We present a novel framework for reconstructing fluid dynamics in real-life scenarios. Our approach leverages sparse view images and incorporates physical priors across long series of frames, resulting in reconstructed fluids with enhanced physical consistency. Unlike previous methods, we utilize a differentiable fluid simulator (DFS) and a differentiable renderer (DR) to exploit global physical priors, reducing reconstruction errors without the need for manual regularization coefficients. We introduce divergence-free Laplacian eigenfunctions (div-free LE) as velocity bases, improving computational efficiency and memory usage. By employing gradient-related strategies, we achieve better convergence and superior results. Extensive experiments demonstrate the effectiveness of our method, showcasing improved reconstruction quality and computational efficiency compared to existing approaches. We validate our approach using both synthetic and real data, highlighting its practical potential.

Background: Effective response and reducing the burden of family care for children with cancer is critical, and China currently lacks a specific assessment tool., Aims: This study aimed to translate and validate the Caregiving Burden Scale for Family Caregivers of Children with Cancer (CBSFC-CC) and then test and implement the tool., Methods: According to the Beaton cross-cultural debugging guide, preliminary Chinese version of CBSFC-CC scale was formed, which was suitable for Chinese language environment and clinical context. Exploratory factor analyses (EFA) and confirmatory factor analyses (CFA) were performed to verify structural validity. Convergent validity, discriminant validity and reliability were also conducted., Results: A total of 529 family caregivers of children with cancer participated in the survey. EFA extracts and combines four factors and explained 65.80% of the total variation. CFA proved that all the goodness-of-fit indicators were acceptable. The Cronbach's alpha of the Chinese version of CBSFC-CC was .96, and the test-retest reliability coefficient was .95. Four dimensions and 29 items were identified in the final Chinese version of CBSFC-CC., Conclusion: The chinese version CBSFC-CC is scientifically reasonable and has good reliability and validity, which can be applied to the investigation of the nursing burden of family caregivers of children with cancer in China., (© 2024. The Author(s).)

The underlying mechanism of the aluminum (Al) on neurotoxicity remains unclear. We explored whether the impairment of hippocampal neurons induced by developmental Al exposure was associated with the m6A RNA modification in mice. In this study, the pregnant female mice were administered 4 mg/mL aluminum-lactate from gestational day (GD) 6 to postnatal day (PND) 21. On PND 21, 10 offsprings per group were euthanized by exsanguination from the abdominal aorta after deep anesthetization. The other offsprings which treated with aluminum-lactate on maternal generation were divided into two groups and given 0 (PND60 a ) and 4 mg/mL (PND60 b ) aluminum-lactate in their drinking water until PND 60. Significant neuronal injuries of hippocampus as well as a reduction in the m6A RNA modification and the expression of methylase were observed at PND 21 and PND 60 a mice. The results indicated that Al-induced developmental neurotoxicity could persist into adulthood despite no sustained Al accumulation. m6A RNA modification had a crucial role in developmental neurotoxicity induced by Al. In addition, Al exposure during the embryonic to adult stages can cause more severe nerve damage and decline of m6A RNA modification. Collectively, these results suggest that the mechanism underlying Al-induced neurotoxicity appears to involve m6A RNA modification., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

The immunosuppressive characteristics and acquired immune resistance can restrain the therapy-initiated anti-tumor immunity. In this work, an antibody free programmed death receptor ligand 1 (PD-L1) downregulator (designated as CeSe) is fabricated to boost photodynamic activated immunotherapy through cyclin-dependent kinase 5 (CDK5) inhibition. Among which, FDA approved photosensitizer of chlorin e6 (Ce6) and preclinical available CDK5 inhibitor of seliciclib (Se) are utilized to prepare the nanomedicine of CeSe through self-assembly technique without drug excipient. Nanoscale CeSe exhibits an increased stability and drug delivery efficiency, contributing to intracellular production of reactive oxygen species (ROS) for robust photodynamic therapy (PDT). The PDT of CeSe can not only suppress the primary tumor growth, but also induce the immunogenic cell death (ICD) to release tumor associated antigens. More importantly, the CDK5 inhibition by CeSe can downregulate PD-L1 to re-activate the systemic anti-tumor immunity by decreasing the tumor immune escape and therapy-induced acquired immune resistance. This work provides an antibody free strategy to activate systemic immune response for metastatic tumor treatment, which may accelerate the development of translational nanomedicine with sophisticated mechanism., (© 2024 Wiley‐VCH GmbH.)

Negative sampling has swiftly risen to prominence as a focal point of research, with wide-ranging applications spanning machine learning, computer vision, natural language processing, data mining, and recommender systems. This surge in interest prompts us to question the fundamental impact of negative sampling: Does negative sampling really matter? Is there a general framework that can incorporate all negative sampling methods? In what fields is it applied? Addressing these questions, we propose a general framework that using negative sampling. Delving into the history of negative sampling, we chart its evolution across five distinct trajectories. We dissect and categorize the strategies used to select negative sample candidates, detailing global, local, mini-batch, hop, and memory-based approaches. Our comprehensive review extends to an analysis of current negative sampling methodologies, systematically grouping them into five classifications: static, hard, GAN-based, Auxiliary-based, and In-batch. Beyond detailed categorization, we explore the practical application of negative sampling across various fields. Finally, we briefly discuss open problems and future directions for negative sampling.

Visual anomaly detection is an essential component in modern industrial manufacturing. Existing studies using notions of pairwise similarity distance between a test feature and nominal features have achieved great breakthroughs. However, the absolute similarity distance lacks certain generalizations, making it challenging to extend the comparison beyond the available samples. This limitation could potentially hamper anomaly detection performance in scenarios with limited samples. This article presents a novel sparse feature representation anomaly detection (SFRAD) framework, which formulates the anomaly detection as a sparse feature representation problem; and notably proposes an anomaly score by orthogonal matching pursuit (ASOMP) as a novel detection metric. Specifically, SFRAD calculates the Gaussian kernel distance between the test feature and its sparse representation in the nominal feature space for anomaly detection. Here, the orthogonal matching pursuit (OMP) algorithm is adopted to achieve the sparse feature representation. Moreover, to construct a low-redundancy memory bank storing the basis features for sparse representation, a novel basis feature sampling (BFS) algorithm is proposed by considering both the maximum coverage and the optimum feature representation simultaneously. As a result, SFRAD incorporates both the advantages of absolute similarity and linear representation; and this enhances the generalization in low-shot scenarios. Extensive experiments on the MVTec anomaly detection (MVTec AD), Kolektor surface-defect dataset (KolektorSDD), Kolektor surface-defect dataset 2 (KolektorSDD2), MVTec logical constraints anomaly detection (MVTec LOCO AD), Visual anomaly (VISA), Modified national institute of standards and technology (MNIST), and CIFAR-10 datasets demonstrate that our proposed SFRAD outperforms the previous methods and achieves state-of-the-art unsupervised anomaly detection performance. Notably, significantly improved outcomes and results have also been achieved on low-shot anomaly detection. Code is available at https://github.com/fanghuisky/SFRAD.

Objective: This is a study to investigate the value of musculoskeletal ultrasound for the early diagnosis of seronegative rheumatoid arthritis (SNRA); and to study the relationship between anti-cyclic citrullinated peptide antibody (anti-CCP) and the occurrence of bone erosion in rheumatoid arthritis (RA) detected by ultrasound., Methods: A total of 101 patients with RA or osteoarthritis (OA) admitted to the First Affiliated Hospital of Anhui Medical University from July 2022 to December 2023 were selected and divided into the SNRA group, the SPRA group, and the OA group. The patients' metacarpophalangeal joints, proximal interphalangeal joints, distal interphalangeal joints, and wrist joints of both hands were ultrasonically examined separately, and the extensor tendon, flexor tendon, synovium, joint surface, joint cavity, and bone surface were observed., Results: The differences in the detection of joint effusion, bone erosion, and joint space narrowing were not statistically significant between SNRA group and OA group (P > .05), the differences in the detection of synovitis and tenosynovitis were statistically significant (P < .05). The mean levels of synovial hyperplasia grade and synovial blood flow grade between SNRA group and OA group were significantly different (P < .05). The differences in synovitis, tenosynovitis, joint effusion, and joint space narrowing were not statistically significant between SNRA and SPRA groups (P > .05), and the differences in bone erosion were statistically significant (P < .05). The mean levels of synovial hyperplasia grade and synovial blood flow grade between SNRA group and SPRA group were significantly different (P < .05). Logistic regression analysis showed that anti-CCP antibody was an influential factor for bone erosion in RA patients (P < .05). The ROC curve was plotted, and the optimal cut-off value of anti-CCP antibody was 356.5 U/mL, at which time the AUC was 0.716, the sensitivity of diagnosing bone erosion was 0.714, the specificity was 0.694, and the Yoden index was 0.408., Conclusion: In summary, ultrasound is helpful for the early diagnosis of SNRA by evaluating the condition of joints, synovium, and tendon sheath, and when anti-CCP antibodies are positive, ultrasound is more likely to detect bone erosion. Ultrasound examination combined with anti-CCP antibody can further observe the joint lesions., (© 2024 American Institute of Ultrasound in Medicine.)

Objective: Anoikis is a kind of programmed cell death that is triggered when cells lose contact with each other or with the matrix. However, the potential value of anoikis-related genes (ARGs) in keloid (KD) has not been investigated. Approach : We downloaded three keloid fibroblast (KF) RNA sequencing (RNA-seq) datasets from the Gene Expression Omnibus (GEO) and obtained 338 ARGs from a search of the GeneCards database and PubMed articles. Weighted correlation network analysis was used to construct the coexpression network and obtain the KF-related ARGs. The LASSO-Cox method was used to screen the hub ARGs and construct the best prediction model. Then, GEO single-cell sequencing datasets were used to verify the expression of hub genes. We used whole RNA-seq for gene-level validation and the correlation between KD immune infiltration and anoikis. Results : Our study comprehensively analyzed the role of ARGs in KD for the first time. The least absolute shrinkage and selection operator (LASSO) regression analysis identified six hub ARGs ( HIF1A , SEMA7A , SESN1 , CASP3 , LAMA3 , and SIK2 ). A large number of miRNAs participate in the regulation of hub ARGs. In addition, correlation analysis revealed that ARGs were significantly correlated with the infiltration levels of multiple immune cells in patients with KD. Innovation : We explored the expression characteristics of ARGs in KD, which is extremely important for determining the molecular pathways and mechanisms underlying KD. Conclusions : This study provides a useful reference for revealing the characteristics of ARGs in the pathogenesis of KD. The identified hub genes may provide potential therapeutic targets for patients. This study provides new ideas for individualized therapy and immunotherapy.

Diaphorina citri serves as the primary vector for ' Candidatus Liberibacter asiaticus ( C Las),' the bacterium associated with the severe Asian form of huanglongbing. C Las-positive D. citri are more fecund than their C Las-negative counterparts and require extra energy expenditure. Therefore, understanding the molecular mechanisms linking metabolism and reproduction is of particular importance. In this study, we found adipokinetic hormone ( DcAKH ) and its receptor ( DcAKHR ) were essential for increasing lipid metabolism and fecundity in response to C Las infection in D. citri . Knockdown of DcAKH and DcAKHR not only resulted in the accumulation of triacylglycerol and a decline of glycogen, but also significantly decreased fecundity and C Las titer in ovaries. Combined in vivo and in vitro experiments showed that miR-34 suppresses DcAKHR expression by binding to its 3' untranslated region, whilst overexpression of miR-34 resulted in a decline of DcAKHR expression and C Las titer in ovaries and caused defects that mimicked DcAKHR knockdown phenotypes. Additionally, knockdown of DcAKH and DcAKHR significantly reduced juvenile hormone (JH) titer and JH signaling pathway genes in fat bodies and ovaries, including the JH receptor, methoprene-tolerant ( DcMet ), and the transcription factor, Krüppel homolog 1 (DcKr-h1 ), that acts downstream of it, as well as the egg development related genes vitellogenin 1-like ( DcVg-1-like ), vitellogenin A1-like ( DcVg-A1-like ) and the vitellogenin receptor ( DcVgR ). As a result, C Las hijacks AKH/AKHR-miR-34-JH signaling to improve D. citri lipid metabolism and fecundity, while simultaneously increasing the replication of C Las, suggesting a mutualistic interaction between C Las and D. citri ovaries., Competing Interests: JL, PH, GB, SW, JH, ST, DW, YH, YC, XN No competing interests declared, (© 2024, Li et al.)

Background: Allergic rhinitis (AR) is a common inflammatory disease of the nasal mucosa that is characterized by symptoms such as sneezing, nasal congestion, nasal itching, and rhinorrhoea. In recent years, acupoint herbal patching (AHP) therapy has gained a growing interest as a potential management option for AR. This systematic review and meta-analysis will evaluate the clinical research evidence on the effectiveness and safety of AHP as a treatment option for AR outside of the Sanfu or Sanjiu days (summer or winter solstice). The results of this review will provide up-to-date evidence-based guidance for healthcare providers and individuals seeking alternative treatments for AR., Methods: A comprehensive search of electronic databases (PubMed, Cochrane Central Register of Controlled Trials (CENTRAL), EMBASE, China National Knowledge Infrastructure (CNKI), CQVIP, Sino-Med, and Wanfang Databases) will be conducted from their inception to June 2023. The inclusion criteria will be limited to randomized controlled trials that evaluate the effectiveness or efficacy of non-Sanfu or non-Sanjiu AHP for AR. The primary outcome measure will be the total nasal symptom score. The methodological quality of included studies will be assessed using the Revised Cochrane risk-of-bias tool for randomized trials (RoB 2), and meta-analyses will be performed using RevMan (V.5.3) statistical software. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach will be used to determine the certainty of evidence., Discussion: This systematic review and meta-analysis will provide valuable insights into the effectiveness and safety of non-Sanfu or non-Sanjiu AHP as a treatment option for AR. The study aims to produce a high-quality review by adhering to PRISMA-P guidelines and using clinical guideline recommended outcome measures. The results of this review may offer additional treatment options for AR patients who seek complementary and alternative therapies, and hold significant implications for future research in this field. Overall, this study has the potential to inform clinical practice and improve patient outcomes., Systematic Review Registration: PROSPERO CRD42022181322., (© 2024. The Author(s).)

The crosstalk between breast cancer cells and tumor associated macrophages (TAMs) greatly contributes to tumor progression and immunosuppression. In this work, cat eye syndrome chromosome region candidate 2 (CECR2) is identified to overexpress in breast cancer patients, which can recognize v-rel avian reticuloendotheliosis viral oncogene homolog A (RelA) and activate nuclear factor κB (NF-κB) to release colony stimulating factor-1 (CSF-1). Pharmacological inhibition of CECR2 by the bromodomain competitor (Bromosporine, Bro) can downregulate CSF-1 to inhibit M2 type TAMs. To amplify the immunotherapeutic effect, a chimeric peptide-based and optical controlled CECR2 competitor (designated as N-PB) is constructed to enhance the nuclear targeted delivery of Bro and initiate an immunogenic cell death (ICD). In vivo results indicate a favorable breast cancer targeting ability and primary tumor suppression effect of N-PB under optical irradiation. Importantly, N-PB downregulates CSF-1 by competitive inhibition of CECR2 and NF-κB(RelA) interactions, thus inhibiting immunosuppressive M2-like TAMs while improving the antitumorigenic M1-like phenotype. Ultimately, the systemic anti-tumor immunity is activated to suppress the metastatic breast cancer in an optical controlled manner. This study provides a promising therapeutic target and reliable strategy for metastatic breast cancer treatment by interrupting immunosuppressive crosstalk between tumor cells and macrophages., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Optic nerve injuries are severely disrupt the structural and functional integrity of the retina, often leading to visual impairment or blindness. Despite the profound impact of these injuries, the molecular mechanisms involved remain poorly understood. In this study, we performed a comprehensive whole-transcriptome analysis of mouse retina samples after optic nerve crush (ONC) to elucidate changes in gene expression and regulatory networks. Transcriptome analysis revealed a variety of molecular alterations, including 256 mRNAs, 530 lncRNAs, and 37 miRNAs, associated with metabolic, inflammatory, signaling, and biosynthetic pathways in the injured retina. The integrated analysis of co-expression and protein-protein interactions identified an active interconnected module comprising 5 co-expressed proteins (Fga, Serpina1a, Hpd, Slc38a4, and Ahsg) associated with the complement and coagulation cascades. Finally, 5 mRNAs (Fga, Serpinala, Hpd, Slc38a4, and Ahsg), 2 miRNAs (miR-671-5p and miR-3057-5p), and 6 lncRNAs (MSTRG. 1830.1, Gm10814, A530013C23Rik, Gm40634, MSTRG.9514.1, A330023F24Rik) were identified by qPCR in the injured retina, and some of them were validated as critical components of a ceRNA network active in 661W and HEK293T cells through dual-luciferase reporter assays. In conclusion, our study provides comprehensive insight into the complex and dynamic biological mechanisms involved in retinal injury responses and highlights promising potential targets to enhance neuroprotection and restore vision., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Objectives: The aim of this study was to develop an assessment tool for automatic detection of dental caries in periapical radiographs using convolutional neural network (CNN) architecture., Methods: A novel diagnostic model named ResNet + SAM was established using numerous periapical radiographs (4278 images) annotated by medical experts to automatically detect dental caries. The performance of the model was compared to the traditional CNNs (VGG19, ResNet-50), and the dentists. The Gradient-weighted Class Activation Mapping (Grad-CAM) technique shows the region of interest in the image for the CNNs., Results: ResNet + SAM demonstrated significantly improved performance compared to the modified ResNet-50 model, with an average F1 score of 0.886 (95% CI 0.855-0.918), accuracy of 0.885 (95% CI 0.862-0.901) and AUC of 0.954 (95% CI 0.924-0.980). The comparison between the performance of the model and the dentists revealed that the model achieved higher accuracy than that of the junior dentists. With the assist of the tool, the dentists achieved superior metrics with a mean F1 score of 0.827 and the interobserver agreement for dental caries is enhanced from 0.592/0.610 to 0.706/0.723., Conclusions: According to the results obtained from the experiments, the automatic assessment tool using the ResNet + SAM model shows remarkable performance and has excellent possibilities in identifying dental caries. The use of the assessment tool in clinical practice can be of great benefit as a clinical decision-making support in dentistry and reduce the workload of dentists., (© 2024. The Author(s) under exclusive licence to Japanese Society for Oral and Maxillofacial Radiology.)

Coccidiosis, which is caused by Eimeria species, results in huge economic losses to the poultry industry. Arbor Acres (AA) broilers and yellow-feathered broilers are the dominant broilers in northern and southern China, respectively. However, their susceptibility to coccidiosis has not been fully compared. In this study, the susceptibility of yellow-feathered broilers, AA broilers and Lohmann pink layers to E. tenella was evaluated based on mortality rate, relative body weight gain rate, intestinal lesion score, oocyst output, anticoccidial index (ACI), and cecum weight and length. The yellow-feathered broilers were shown to produce significantly fewer oocysts with higher intestinal lesion score compared to AA broilers, which had the highest growth rates and ACI scores. Subsequently, changes in the cecal microbiota of the 3 chicken lines before and after high-dose infection (1 × 10 4 oocysts) with E. tenella were determined by 16S rRNA sequencing. The results showed that composition of the microbiota changed dramatically after infection. The abundance of Firmicutes and Bacteroidetes in the infected chickens decreased, and Proteobacteria increased significantly among the different chicken lines. At the genus level, Escherichia increased significantly in all 3 groups of infected chickens, but Lactobacillus decreased to 0% in the infected yellow-feathered broilers. The results of the study indicate that the susceptibility to E. tenella varies among the 3 chicken lines, and that changes in intestinal microbiota by E. tenella-infection among the different chicken lines had a similar trend, but to different degrees. This study provides basic knowledge of the susceptibility in the 3 chicken lines, which can be helpful for the control and prevention of coccidiosis., Competing Interests: DISCLOSURES The authors declare no conflicts of interest., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

The electrocatalytic CO 2 reduction reaction (CO 2 RR) is a sustainable route for converting CO 2 into value-added fuels and feedstocks, advancing a carbon-neutral economy. The electrolyte critically influences CO 2 utilization, reaction rate and product selectivity. While typically conducted in neutral/alkaline aqueous electrolytes, the CO 2 RR faces challenges due to (bi)carbonate formation and its crossover to the anolyte, reducing efficiency and stability. Acidic media offer promise by suppressing these processes, but the low Faradaic efficiency, especially for multicarbon (C 2+ ) products, and poor electrocatalyst stability persist. The effective regulation of the reaction environment at the cathode is essential to favor the CO 2 RR over the competitive hydrogen evolution reaction (HER) and improve long-term stability. This review examines progress in the acidic CO 2 RR, focusing on reaction environment regulation strategies such as electrocatalyst design, electrode modification and electrolyte engineering to promote the CO 2 RR. Insights into the reaction mechanisms via in situ/operando techniques and theoretical calculations are discussed, along with critical challenges and future directions in acidic CO 2 RR technology, offering guidance for developing practical systems for the carbon-neutral community., (© 2024 Wiley-VCH GmbH.)

Wool plays an irreplaceable role in the lives of livestock and the textile industry. The variety of hair quality and shape leads to the diversity of its functions and applications, and the finer wool has a higher economic value. In this study, 10 coarse and 10 fine ordos fine wool sheep skin samples were collected for RNA-seq, and coarse and fine skin/hair follicle RNA-seq datasets of other five animal breeds were obtained from NCBI. Weighted gene co-expression network analysis showed that the common genes were clustered into eight modules. Similar gene expression patterns in sheep and rabbits with the same wool types, different gene expression patterns in animal species with different hair types, and brown modules were significantly correlated with species and breeds. GO and KEGG enrichment analyses showed that, most genes in the brown module associated with hair follicle development. Hence, gene expression patterns in skin tissues may determine hair morphology in animal. The analysis of differentially expressed genes revealed that 32 highly expressed candidate genes associated with the wool fineness of Ordos fine wool sheep. Among them, KAZALD1 (grey module), MYOC (brown module), C1QTNF6 (brown module), FOS (tan module), ITGAM, MX2, MX1, and IFI6 genes have been reported to be involved in the regulation of the hair follicle cycle or hair loss. Additionally, 12 genes, including KAZALD1, MYOC, C1QTNF6, and FOS, are differentially expressed across various animal breeds and species. The above results suggest that different sheep breeds share a similar molecular regulatory basis of wool fineness. Finally, the study provides a theoretical reference for molecular breeding of sheep breeds as well as for the investigation of the origin and evolution of animal hair., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Pu, Ma, Zhao, Tang, Lu, Liu, Wang, Cen, Wu and Fu.)

DNA nanostructures with diverse biological functions have made significant advancements in biomedical applications. However, a universal strategy for the efficient production of DNA nanostructures is still lacking. In this work, a facile and mild method is presented for self-assembling polyethylenimine-modified carbon dots (PEI-CDs) and DNA into nanospheres called CANs at room temperature. This makes CANs universally applicable to multiple biological applications involving various types of DNA. Due to the ultra-small size and strong cationic charge of PEI-CDs, CANs exhibit a dense structure with high loading capacity for encapsulated DNA while providing excellent stability by protecting DNA from enzymatic hydrolysis. Additionally, Mg 2+ is incorporated into CANs to form Mg@CANs which enriches the performance of CANs and enables subsequent biological imaging applications by providing exogenous Mg 2+ . Especially, a DNAzyme logic gate system that contains AND and OR Mg@CANs is constructed and successfully delivered to tumor cells in vitro and in vivo. They can be specifically activated by endogenic human apurinic/apyrimidinic endonuclease 1 and recognize the expression levels of miRNA-21 and miRNA-155 at tumor sites by logic biocomputing. A versatile pattern for delivery of diverse DNA and flexible logic circuits for multiple miRNAs imaging are developed., (© 2024 Wiley‐VCH GmbH.)

Syntaxin of plant (SYP) plays a crucial role in SNARE-mediated membrane trafficking during endocytic and secretory pathways, contributing to the regulation and execution of plant immunity against pathogens. Verticillium wilt is among the most destructive fungal diseases affecting cotton worldwide. However, information regarding SYP family genes in cotton is scarce. Through genome-wide identification and transcriptome profiling, we identified GhSYP121, a Qa SNARE gene in Gossypium hirsutum. GhSYP121 is notably induced by Verticillium dahliae, the causal agent of Verticillium wilt in cotton, and acts as a negative regulator of defense against V. dahliae. This is evidenced by the reduced resistance of GhSYP121-deficient cotton and the increased susceptibility of GhSYP121-overexpressing lines. Furthermore, the activation of the salicylic acid (SA) pathway by V. dahliae is inversely correlated with the expression level of GhSYP121. GhSYP121 interacts with its cognate SNARE component, GhSNAP33, which is required for the penetration resistance against V. dahliae in cotton. Collectively, GhSYP121, as a member of the cotton SNARE complex, is involved in regulating the SA pathway during plant defense against V. dahliae. This finding enhances our understanding of the potential role of GhSYP121 in these distinct pathways that contribute to plant defense against V. dahliae infection., (© 2024 Wiley Periodicals LLC.)

In droplet-based single-cell and single-nucleus RNA-seq assays, systematic contamination of ambient RNA molecules biases the quantification of gene expression levels. Existing methods correct the contamination for all genes globally. However, there lacks specific evaluation of correction efficacy for varying contamination levels. Here, we show that DecontX and CellBender under-correct highly contaminating genes, while SoupX and scAR over-correct lowly/non-contaminating genes. Here, we develop scCDC as the first method to detect the contamination-causing genes and only correct expression levels of these genes, some of which are cell-type markers. Compared with existing decontamination methods, scCDC excels in decontaminating highly contaminating genes while avoiding over-correction of other genes., (© 2024. The Author(s).)

Continuous and long-term use of traditional and new pesticides can result in cross-resistance among pest populations in different fields. Study on the mechanism of cross-resistance and related genes will help resistance management and field pest control. In this study, the pesticide-resistance mechanism in Spodoptera frugiperda (FAW) was studied with field populations in 3 locations of South China. Field FAW populations were highly resistant to traditional insecticides, chlorpyrifos (organophosphate) and deltamethrin (pyrethroid), and had higher levels of cytochrome P450 activity than a non-resistant laboratory strain. Inhibition of P450 activity by piperonyl butoxide significantly increased the sensitivity of resistant FAW in 3 locations to chlorpyrifos, deltamethrin and chlorantraniliprole (amide), a new type of insecticide, suggesting that P450 detoxification is a critical factor for insecticide resistance in field FAW populations. Transcriptomic analysis indicated that 18 P450 genes were upregulated in the field FAW populations collected in 3 regions and in 2 consecutive years, with CYP6a13, the most significantly upregulated one. Knockdown of CYP6a13 messenger RNA by RNA interference resulted in an increased sensitivity to the 3 tested insecticides in the field FAW. Enzyme activity and molecular docking analyses indicated that CYP6a13 enzyme was able to metabolize the 3 tested insecticides and interact with 8 other types of insecticides, confirming that CYP6a13 is a key cross-resistance gene with a wide range of substrates in the field FAW populations across the different regions and can be used as a biomarker and target for management of FAW insecticide resistance in fields., (© 2024 Institute of Zoology, Chinese Academy of Sciences.)

Accurate classification of tumor cells is of importance for cancer diagnosis and further therapy. In this study, we develop multimolecular marker-activated transmembrane DNA computing systems (MTD). Employing the cell membrane as a native gate, the MTD system enables direct signal output following simple spatial events of "transmembrane" and "in-cell target encounter", bypassing the need of multistep signal conversion. The MTD system comprises two intelligent nanorobots capable of independently sensing three molecular markers (MUC1, EpCAM, and miR-21), resulting in comprehensive analysis. Our AND-AND logic-gated system (MTD AND-AND ) demonstrates exceptional specificity, allowing targeted release of drug-DNA specifically in MCF-7 cells. Furthermore, the transformed OR-AND logic-gated system (MTD OR-AND ) exhibits broader adaptability, facilitating the release of drug-DNA in three positive cancer cell lines (MCF-7, HeLa, and HepG2). Importantly, MTD AND-AND and MTD OR-AND , while possessing distinct personalized therapeutic potential, share the ability of outputting three imaging signals without any intermediate conversion steps. This feature ensures precise classification cross diverse cells (MCF-7, HeLa, HepG2, and MCF-10A), even in mixed populations. This study provides a straightforward yet effective solution to augment the versatility and precision of DNA computing systems, advancing their potential applications in biomedical diagnostic and therapeutic research.

Background: The etiology of gallstone disease (GSD) has not been fully elucidated. Consequently, the primary objective of this study was to scrutinize and provisionally authenticate the distinctive expression profiles of long non-coding RNAs (lncRNAs) and messenger RNAs (mRNAs) in GSD., Methods: RiboNucleic Acid (RNA) sequencing was used on four paired human gallbladder samples for the purpose of this study. Differentially expressed lncRNAs (DElncRNAs) and mRNAs (DEmRNAs) were identified and subjected to analysis of their biological functions. The Pearson's correlation coefficients between DElncRNAs and DEmRNAs were computed to construct a co-expression network delineating their associations. Furthermore, both cis- and trans-regulatory networks of selected lncRNAs were established and visualized. Additionally, a competing endogenous RNA (ceRNA) regulatory network was constructed. To validate the RNA-sequencing data, we performed a Quantitative Real-time Polymerase Chain Reaction (RT-qPCR) on 10 paired human gallbladder samples, assessing the expressions of the top 4 DEmRNAs and DElncRNAs in gallstone and control samples., Results: A total of 934 DEmRNAs and 304DElncRNAs were successfully identified. Functional enrichment analysis indicated a predominant involvement in metabolic-related biological functions. Correlation analysis revealed a strong association between the expressions of 597 DEmRNAs and 194 DElncRNAs. Subsequently, both a cis-lncRNA-mRNA and a trans-lncRNA-Transcription Factor (TF)-mRNA regulatory network were meticulously constructed. Additionally, a ceRNA network, comprising of 24 DElncRNAs, 201 DEmRNAs, and 120 predicted miRNAs, was established. Furthermore, using RT-qPCR, we observed significant upregulation of AC004692.4, HECW1-IT1, SFRP4, and COMP, while LINC01564, SLC26A3, RP1-27K12.2, and GSTA2 exhibited marked downregulation in gallstone samples. Importantly, these findings were consistent with the sequencing., Conclusion: We conducted a screening process to identify DElncRNAs and DEmRNAs in GSD. This approach contributes to a deeper understanding of the genetic factors involved in the etiology of gallstones., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Sun, Xu, Luo, Li, Chen, Cen and Xu.)

Recent studies have initially shown that MRI-based rim enhancement associates with poor prognosis in hepatocellular carcinoma (HCC) patients, but their sample sizes are small, leading to a necessary of comprehensive analyses to make a relatively solid statement. Thus, this meta-analysis aimed to summarize the correlation between MRI-based rim enhancement and prognosis in HCC patients. Until March 2023, a literature search was conducted on Web of Science, PubMed, EMBASE, Cochrane, CNKI, Wangfang, and CQVIP databases in order to identify studies that report the correlation between MRI-based rim enhancement and the prognosis of HCC patients. MRI-based rim enhancement and prognostic data were extracted and analyzed. In our study, eight studies containing 1816 HCC patients were analyzed. Generally, the presence of MRI-based rim enhancement was related to shortened disease-free survival (DFS) [hazard ratio (HR): 2.77, 95% confidence interval (CI): 2.11-3.62, P < 0.001], and worse overall survival (OS) (HR: 5.43, 95% CI: 2.14-13.79, P < 0.001). While no other prognostic data could be retrieved. Funnel plots, Begg's test, and Egger's test all indicated that no publication bias existed; and the risk score by Newcastle-Ottawa Scale criteria ranged from 7-9 points, suggesting a generally low risk of bias. Meanwhile, the sensitivity analysis showed that the significant findings did not change by omitting each study. Then, subgroup analyses revealed that no matter stratified by tumor size, treatment option, or sample size, rim enhancement was linked with unsatisfied DFS (all P < 0.05). Conclusively, MRI-based rim enhancement could effectually estimate poor survival in HCC patients, indicating its good prognostic value., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

Objective: We conducted this study to determine the impact of serum glycosaminoglycan hyaluronan (HA) on the prognosis of coronavirus disease 2019 (COVID-19)., Methods: A total of 497 hospitalized patients with COVID-19 were included. Patients were divided into two subgroups based on the severity of infection: mild (n=344) and severe (n=153). The levels of HA, lymphocyte count, C-reactive protein (CRP), ferritin, interleukin 6 (IL-6), and D-dimer were measured and the correlation of these parameters with the prognosis of COVID-19 was assessed., Results: The mean HA level of the severe group was significantly higher than that of the mild group (204.4 ng/mL versus 850.6 ng/mL, P <0.01). In receiver operating characteristic curve analysis, an HA level ≥607.8 ng/mL predicted severe COVID-19 with a sensitivity of 62.3% and specificity of 88.6%. Multivariate regression analysis demonstrated that serum HA level was a significant predictor of disease severity (odds ratio=60.56, P <0.01)., Conclusion: Our findings show that higher serum HA concentrations are associated with severe COVID-19 disease. Early analysis of HA level in patients with COVID-19 might effectively predict disease severity., (© 2024 by the Association of Clinical Scientists, Inc.)

A systemic treatment strategy is urgently demanded to suppress the rapid growth and easy metastasis characteristics of breast cancer. In this work, a chimeric peptide-engineered self-delivery nanomedicine (designated as ChiP-CeR) for photodynamic-triggered breast cancer immunotherapy by macrophage polarization. Among these, ChiP-CeR is composed of the photosensitizer of chlorine e6 (Ce6) and the TLR7/8 agonist of lmiquimod (R837), which is further modified with tumor matrix targeting peptide (Fmoc-K(Fmoc)-PEG 8 -CREKA. ChiP-CeR is preferred to actively accumulate at the tumor site via specific recognition of fibronectin, which can eradicate primary tumor growth through photodynamic therapy (PDT). Meanwhile, the destruction of primary tumors would trigger immunogenic cell death (ICD) effects to release high-mobility group box-1(HMGB1) and expose calreticulin (CRT). Moreover, ChiP-CeR can also polarize M2-type tumor-associated macrophages (TAMs) into M1-type TAMs, which can activate T cell antitumor immunity in combination with ICD. Overall, ChiP-CeR possesses superior antitumor effects against primary and lung metastatic tumors, which provide an applicable nanomedicine and a feasible strategy for the systemic management of metastatic breast cancer., (© 2023 Wiley‐VCH GmbH.)

The 2D semiconductors are an ideal platform for exploration of bosonic fluids composed of coupled photons and collective excitations of atoms or excitons, primarily due to large excitonic binding energies and strong light-matter interaction. Based on first-principles calculations, it is demonstrated that the phonon polaritons formed by two infrared-active phonon modes in monolayer MoSi 2 N 4 and WSi 2 N 4 possess ultra-high confinement factors of around ≈10 5 and 10 3 , surpassing those of conventional polaritonic thin-film materials by two orders of magnitude. It is observed that the first bright exciton possesses a substantial binding energies of 750 and 740 meV in these two monolayers, with the radiative recombination lifetimes as long as 25 and 188 ns, and the Rabi splitting of the formed cavity-exciton polaritons reaching 373 and 321 meV, respectively. The effective masses of the cavity exciton polaritons are approximately 10 -5 m e , providing the potential for high-temperature quantum condensation. The ultra-confined and ultra-low-loss phonon polaritons, as well as strongly-coupled cavity exciton polaritons with ultra-small polaritonic effective masses in these two monolayers, offering the flexible control of light at the nanoscale, probably leading to practical applications in nanophotonics, meta-optics, and quantum materials., (© 2023 The Authors. Advanced Science published by Wiley‐VCH GmbH.)

BACKGROUND While many studies have been conducted on sugammadex sodium and neostigmine in patients undergoing general anesthesia, few have explored their effects in patients with interstitial lung diseases (ILDs). MATERIAL AND METHODS Sixty-three patients who underwent transbronchial cryobiopsy under general anesthesia were enrolled in a prospective randomized study. The patients were randomly divided into 2 groups: neostigmine combined with atropine group (group C, n=32) and sugammadex group (group S, n=31). Induction and maintenance of anesthesia were the same in both groups. Patients received rocuronium during anesthesia. At the end of the procedure, when the T2 of the train-of-four stimulation technique (TOF) monitoring appeared, neostigmine 0.04 mg/kg combined with atropine 0.02 mg/kg was injected intravenously in group C, and sodium sugammadex 2 mg/kg was injected intravenously in group S. Time from administration of muscle relaxant antagonist to recovery of TOF ratio (TOFr) to 0.9 and extubation time were recorded. The residual rate of neuromuscular blockade at 1, 3, 5, 7, and 10 min after extubation was calculated. RESULTS Compared to group C, group S had a significantly shorter recovery time of TOFr to 0.9 (4.0[2.0] min vs 14.0[11.0] min, P<0.001) and extubation time (4.0[3.0] min vs 11.0[7.0] min, P<0.001). The residual rate of neuromuscular blockade was remarkably lower in group S than in group C at 3, 5, and 7 min after extubation (3.2% vs 31%, 0% vs 25%, 0% vs 6%, P<0.05). CONCLUSIONS Sugammadex is more effective than neostigmine in reversing the muscle-relaxant effect of rocuronium bromide in patients with ILDs.