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Monascus pigments (MPs) have been used as natural food pigments for many years. There is a high demand for Monascus red pigments (MRPs) to enhance color and for antibacterial and cancer prevention therapies in food and medicine. Most MRPs are not water soluble, and the yield of water‐soluble MRPs is naturally low. On the other hand, water‐soluble MRP is more cost effective for application in industrial mass production. Therefore, it is important to improve the yield of water‐soluble MRPs. Environmental factors have a significant influence on the synthesis of water‐soluble MRPs, which is crucial for the development of industrial production of water‐soluble MRPs. This review introduces the biosynthetic pathways of water‐soluble MRPs and summarizes the effects of environmental factors on the yield of water‐soluble MRPs. Acetyl coenzyme A (acetyl‐CoA) is a precursor for MPs synthesis. Carbon and nitrogen sources and the carbon/nitrogen ratio can impact MP production by regulating the metabolic pathway of acetyl‐CoA. Optimization of fermentation conditions to change the morphology of Monascus can stimulate the synthesis of MPs. The appropriate choice of nitrogen sources and pH values can promote the synthesis of MRPs from MPs. Additives such as metal ions and non‐ionic surfactants can affect the fluidity of Monascus cell membrane and promote the transformation of MRPs into water‐soluble MRPs. This review will lay the foundation for the industrial production of water‐soluble MRPs. © 2024 Society of Chemical Industry. [ABSTRACT FROM AUTHOR]

Objective: We sought to evaluate urate‐lowering therapy (ULT) adherence and treatment‐to‐target (T2T) serum uric acid (SUA) levels among older adults with gout starting ULT. Methods: We performed a population‐based retrospective cohort study in Ontario, Canada in patients with gout aged ≥66 years newly dispensed ULT between 2010 and 2019. We defined successful T2T as patients having SUA levels <360 μmol/L (6 mg/dL) within 12 months after ULT dispensation. We also assessed adherence to ULT. Multilevel logistic regression clustered by ULT prescriber evaluated patient, physician, and prescription factors associated with reaching target SUA levels. Results: Among 44,438 patients (mean ± SD age 76.0 ± 7.3 years; 64.4% male), 30,057 (67.6%) patients had ≥1 SUA test completed. Overall, 52.3% patients reached SUA target within 12 months, improving from 45.2% in 2010 to 61.2% in 2019 (P < 0.0001). ULT adherence was 55.3% overall and improved annually. Key factors associated with achieving T2T included febuxostat treatment (odds ratio [OR] 11.40, 95% confidence interval [95% CI] 5.10–25.43) (was only dispensed in 88 patients), ULT adherence (OR 5.17, 95% CI 4.89–5.47), allopurinol starting doses >50 mg (OR 2.53, 95% CI 2.14–2.99), colchicine/oral glucocorticoids co‐prescription (OR 1.24, 95% CI 1.14–1.34), and ULT prescription from a rheumatologist. Conclusion: Only 52.3% of patients achieved an optimal SUA level within 1 year of ULT initiation. ULT adherence was suboptimal, although improving over time. ULT adherence and higher allopurinol starting doses had the strongest associations of achieving a target SUA level. This study highlights room for improvement in gout management and potential strategies to address care gaps. [ABSTRACT FROM AUTHOR]

Overcoming tumor apoptosis resistance is a major challenge in enhancing cancer therapy. Pyroptosis, a lytic form of programmed cell death (PCD) involving inflammasomes, Gasdermin family proteins, and cysteine proteases, offers potential in cancer treatment. While photodynamic therapy (PDT) can induce pyroptosis by generating reactive oxygen species (ROS) through the activation of photosensitizers (PSs), many PSs lack specific subcellular targets and are limited to the first near‐infrared window, potentially reducing treatment effectiveness. Therefore, developing effective, deep‐penetrating, organelle‐targeted pyroptosis‐mediated phototherapy is essential for cancer treatment strategies. Here, we synthesized four molecules with varying benzene ring numbers in thiopyrylium structures to preliminarily explore their photodynamic properties. The near‐infrared‐II (NIR‐II) PS Z1, with a higher benzene ring count, exhibited superior ROS generation and mitochondria‐targeting abilities, and a large Stokes shift. Through nano‐precipitation method, Z1 nanoparticles (NPs) also demonstrated high ROS generation (especially type‐I ROS) upon 808 nm laser irradiation, leading to efficient mitochondria dysfunction and combined pyroptosis and apoptosis. Moreover, they exhibited exceptional tumor‐targeting ability via NIR‐II fluorescence imaging (NIR‐II FI) and photoacoustic imaging (PAI). Furthermore, Z1 NPs‐mediated phototherapy effectively inhibited tumor growth with minimal adverse effects. Our findings offer a promising strategy for cancer therapy, warranting further preclinical investigations in PDT. [ABSTRACT FROM AUTHOR]

A green corrosion inhibitor was prepared from the bio‐based platform compound 5‐hydroxymethylfurfural through a green synthetic route, which avoid the use of toxic reagent. The inhibition performance and mechanism of this compound for the corrosion of mild steel in 0.1 M HCl was investigated by using the weight loss experiments, polarization measurements, EIS measurements and quantum chemical calculations. The corrosion inhibition efficiency by weight loss measurement (ηWLM%) of this inhibitor can reach up to 90.3 % at 303 K with 1.2 mM concentration. Moreover, the electrochemical experiments revealed that this corrosion inhibitor acts as a mixed‐type inhibitor. Thermodynamic studies gave the values of the standard Gibbs free energy ΔGads0 ${{\rm \Delta }{G}_{ads}^{0}}$ , fall within the range of −20 kJ/mol to −40 kJ/mol, suggested the adsorption of this compound is a spontaneous process involving both physisorption and chemisorption. In addition, quantum chemical calculations were conducted to further validate the formation of an effective absorption layer by this inhibitor on metal surfaces, which showed that the electron density iso‐surfaces of HOMO was mainly distributed on chloride ions, while LUMO tended to be distributed on furan rings and aldehyde groups. Besides, the other quantum chemical parameters of this inhibitor were also calculated to explore the molecular activity, such as, the molecular volume (ν, 333.105 Å), global hardness (η, 4.706 eV), global softness (σ, 0.2125 eV), electronegativity (χ, 4.93 eV), dipolemoment (μ, 13.1429 D) and vertical ionization energy (VIE, 7.2646 eV). [ABSTRACT FROM AUTHOR]

Objectives Methods Results Conclusions This study investigated the accuracy of robotic computer‐assisted implant surgery (r‐CAIS) for immediate implant placement.Twenty cases with 20 implant sites were selected based on predefined inclusion criteria. The preparation of the implant bed and implant placement followed the standardized dental implant robotic surgery protocol. Postoperative cone‐beam computed tomography scans were conducted to assess possible discrepancies between actual and planned implant positions.The r‐CAIS technology for immediate implant placement exhibited a mean global coronal deviation of 0.71 ± 0.27 mm (95% CI: 0.58–0.83 mm), a mean global apical deviation of 0.69 ± 0.26 mm (95% CI: 0.56–0.81 mm), and an angular deviation of 1.27 ± 0.47° (95% CI: 1.05–1.49°). A substantial number of deviations were observed buccally at both coronal (90%) and apical (95%) levels, with a consistent tendency for buccal deviation.The r‐CAIS technology proved a promising approach for immediate implantation in the anterior region, with satisfactory clinical outcomes. However, an optimized surgical protocol for r‐CAIS technology is required for particular implant sites like extraction sockets or bone defects. [ABSTRACT FROM AUTHOR]

Precisely controlling the product selectivity of a reaction is an important objective in organic synthesis. α‐Ketoamides are vital intermediates in chemical transformations and privileged motifs in numerous drugs, natural products, and biologically active molecules. The selective synthesis of α‐ketoamides from feedstock chemicals in a safe and operationally simple manner under mild conditions is a long‐standing catalysis challenge. Herein, an unprecedented TBD‐switched Pd‐catalyzed double isocyanide insertion reaction for assembling ketoamides in aqueous DMSO from (hetero)aryl halides and pseudohalides under mild conditions is reported. The effectiveness and utility of this protocol are demonstrated by its diverse substrate scope (93 examples), the ability to late‐stage modify pharmaceuticals, scalability to large‐scale synthesis, and the synthesis of pharmaceutically active molecules. Mechanistic studies indicate that TBD is a key ligand that modulates the Pd‐catalyzed double isocyanide insertion process, thereby selectively providing the desired α‐ketoamides in a unique manner. In addition, the imidoylpalladium(II) complex and α‐ketoimine amide are successfully isolated and determined by X‐ray analysis, confirming that they are probable intermediates in the catalytic pathway. [ABSTRACT FROM AUTHOR]

Despite various efforts to optimize the near‐infrared (NIR) performance of perylene diimide (PDI) derivatives for bio‐imaging, convenient and efficient strategies to amplify the fluorescence of PDI derivatives in biological environment and the intrinsic mechanism studies are still lacking. Herein, we propose an alkyl‐doping strategy to amplify the fluorescence of PDI derivative‐based nanoparticles for improved NIR fluorescence imaging. The developed PDI derivative, OPE‐PDI, shows much brighter in n‐Hexane (HE) compared with that in other organic media, and the excited state dynamics investigation experimentally elucidates the solvent effect‐induced suppression of intermolecular energy transfer and intramolecular nonradiative decay as the underlying mechanism for the fluorescence improvement. Theoretical calculations reveal the lowest reorganization energies of OPE‐PDI in HE among various solvents, indicating the effectively suppressed conformational relaxation to support the strongest radiative decay. Inspired by this, an alkyl atmosphere mimicking HE is constructed by incorporating the octadecane into OPE‐PDI‐based nanoparticles, permitting up to 3‐fold fluorescence improvement compared with the counterpart nanoparticles. Owing to the merits of high brightness, anti‐photobleaching, and low biotoxicity for the optimal nanoparticles, they have been employed for probing and long‐term monitoring of tumor. This work highlights a facile strategy for the fluorescence enhancement of PDI derivative‐based nanoparticles. [ABSTRACT FROM AUTHOR]

Motor learning (ML), which plays a fundamental role in growth and physical rehabilitation, involves different stages of learning and memory processes through different brain regions. However, the neural mechanisms that underlie ML are not sufficiently understood. Here, a previously unreported neuronal projection from the dorsal hippocampus (dHPC) to the zona incerta (ZI) involved in the regulation of ML behaviors is identified. Using recombinant adeno‐associated virus, the projections to the ZI are surprisingly identified as originating from the dorsal dentate gyrus (DG) and CA1 subregions of the dHPC. Furthermore, projection‐specific chemogenetic and optogenetic manipulation reveals that the projections from the dorsal CA1 to the ZI play key roles in the acquisition and consolidation of ML behaviors, whereas the projections from the dorsal DG to the ZI mediate the retrieval/retention of ML behaviors. The results reveal new projections from the dorsal DG and dorsal CA1 to the ZI involved in the regulation of ML and provide insight into the stages over which this regulation occurs. [ABSTRACT FROM AUTHOR]

The paper proposes a single antenna that can generate dual‐mode plane spiral orbital angular momentum (PS‐OAM) beams. Six Vivaldi antennas placed in a tangential circular array make up the antenna, and the antenna is etched onto a substrate material and has a flat design, allowing for easy integration with other system components. The neighbouring ports of the antenna elements have phase differences, so phase‐shifting in the feeding network is unnecessary. When fed with the same phase and amplitude, the antenna can produce PS‐OAM beams with mode +1 at 7 GHz and mode +2 at 14 GHz, and the measured purity is 80.6% and 63%, respectively. The method may provide a new way to produce multi‐mode orbital angular momentum. [ABSTRACT FROM AUTHOR]

Background: In vitro single‐cell experiments may yield inconsistent results compared to clinical trials. To enhance the reliability of cosmetic active ingredient screening, a coculture model of B16F10‐HaCaT cells was established in vitro based on the structural characteristics of human skin, thereby improving the credibility of experimental outcomes. Currently, most cosmetic whitening additives primarily target simple efficacy goals such as inhibiting tyrosinase activity or melanin transfer. Therefore, investigating novel and efficient whitening additives has become a prominent research focus. Objectives: The aim is to establish an in vitro cell coculture model for more reliable experimental results and investigate the mechanism by which Paeonia lactiflora Pall seeds oil inhibits melanin production and transfer. Methods: The impact of different concentrations of Paeonia lactiflora Pall seeds oil on cocultured cell proliferation rate was assessed using cck8 assay. Tyrosinase inhibition ability in cocultured cells was tested using levodopa as a substrate. Melanin production inhibition ability in coculture cells was evaluated by lysing cells with sodium hydroxide. The effect of Paeonia lactiflora Pall seeds oil on dendrite‐related gene expression levels was examined through qPCR analysis. Additionally, Western blotting was employed to study the effect of Paeonia lactiflora Pall seeds oil on dendrite‐related protein expression levels. Results: Different concentrations of Paeonia lactiflora Pall seeds oil did not affect the proliferation activity of cocultured cells. A specific concentration of α‐MSH increased cell tyrosinase activity, cellular melanin content, as well as Rac1, Cdc42, and PAR‐2 gene and protein expression related to dendritic formation. Treatment with a certain concentration of Paeonia lactiflora Pall seeds oil resulted in decreased tyrosinase activity and melanin content in cells along with downregulated expression levels of Rac1, Cdc42, and PAR‐2 genes and proteins associated with dendritic formation. Conclusions: Paeonia lactiflora Pall seeds oil at specific concentrations exhibits the ability to inhibit tyrosinase activity, decrease melanin content, and possesses the potential to impede melanin transfer. [ABSTRACT FROM AUTHOR]

BACKGROUND: Folate is crucial for maintaining health, but humans are unable to synthesize folate and need to obtain it from food. Lactiplantibacillus plantarum can produce the necessary vitamin B for the human body, including folate. Whole genome sequencing technology can clarify the physiological characteristics of folate production in Lactiplantibacillus plantarum. In order to explore new Lactiplantibacillus plantarum that produce folate, the folate production and probiotic characteristics of Lactiplantibacillus plantarum ZFM55 isolated from infant feces were investigated, and whole genome sequencing was performed. RESULTS: The folate synthesis ability of Lactiplantibacillus plantarum ZFM55 were measured, and its total folate production was 299.72 ± 28.81 ng mL−1. Subsequently, its probiotic properties were explored. The antibacterial test showed that its inhibition zone diameter against Staphylococcus aureus and Salmonella typhimurium was 15.5 ± 0.82 mm and 13.88 ± 0.98 mm, respectively. The tolerance test results indicated that it maintained good activity in simulated gastrointestinal tract and bile salt environments. In vitro intestinal simulation experiments had confirmed that Lactiplantibacillus plantarum ZFM55 can increase the abundance of beneficial bacteria such as Bifidobacteria in the intestine and inhibit the growth of harmful bacteria such as Escherichia_Shigella. Genomic sequencing indicated that the genetic material of Lactiplantibacillus plantarum ZFM55 contains one chromosome and three plasmids, and it has 20 genes related to folate synthesis, which explains its ability to produce folate. CONCLUSION: This study reports a new potential probiotic that produces folate, and provides ideas for exploring probiotics with specific probiotic characteristics. © 2024 Society of Chemical Industry. [ABSTRACT FROM AUTHOR]

Boron and nitrogen can enter the carbon lattice and provide structural disorder, porous structure, and active sites for better catalyst dispersions and activity. Herein, Bi2Mo2.5(S,O)10 oxysulfide (BiMoOS) anchored on unmodified and surface‐modified activated carbon (AC) via B and N doping is synthesized for efficient PHER, aiming that B and N doping into carbon framework can modify the surface textural features which act as anchoring sites for the host Bi2Mo2.5(S,O)10 and boost its photocatalytic activity by increasing specific surface area via preventing aggregation through a uniform distribution. Thus, the BiMoOS@B─N─AC catalyst achieved excellent stability and PHER performance (564.2 µmol h−1 H2 under visible light). The doped B and N in AC create structural disorder/defects, active sites and induce electron delocalization in B─N─AC, used as the anchoring sites for BiMoOS catalysts and stimulate the adsorption and activation kinetics of the H2O molecules, and also provide a highly conductive network that enhances charge transport and stability of BiMoOS@B─N─AC. With the advantages of the modified B─N─AC, the oxygen vacancy‐anchored BiMoOS exhibited superb PHER. Hence, B and N co‐doping into the carbon lattice is a promising approach to enriching the anchoring site for boosting metallic nanocatalyst stability and catalytic performance. [ABSTRACT FROM AUTHOR]

While share pledging is a widespread leveraged financing practice in global stock markets, its potential impact on firms' exposure to market risk remains a topic of concern. In the context of the Chinese market, this study investigates the relationship between insiders' share pledging pressure and stock liquidity risk, with a particular focus on stock liquidity commonality. Using data from Chinese firms listed between 2009 and 2022, we find a positive correlation between heightened share pledging pressure and increased stock liquidity commonality. To precisely capture the margin call pressure arising from share pledging, we introduce an innovative method that considers both the price at which shares are pledged and their subsequent price dynamics. This relationship persists after addressing endogeneity concerns. Furthermore, we find that firms under significant share pledging pressure often resort to earnings manipulation, which exacerbates stock liquidity commonality. The findings underscore the significance of understanding the risks and impacts of share pledging in terms of liquidity risk. Insiders who utilize share pledging as a financing channel face a delicate balance between the benefits of expanded funding sources and the risks of losing control due to sustained stock price declines. This study provides valuable insights for investors, policymakers, and regulatory authorities in managing the potential liquidity risks associated with share pledging activities in the Chinese market. [ABSTRACT FROM AUTHOR]

Halogenation of Y‐series small‐molecule acceptors (Y‐SMAs) is identified as an effective strategy to optimize photoelectric properties for achieving improved power‐conversion‐efficiencies (PCEs) in binary organic solar cells (OSCs). However, the effect of different halogenation in the 2D‐structured large π‐fused core of guest Y‐SMAs on ternary OSCs has not yet been systematically studied. Herein, four 2D‐conjugated Y‐SMAs (X‐QTP‐4F, including halogen‐free H‐QTP‐4F, chlorinated Cl‐QTP‐4F, brominated Br‐QTP‐4F, and iodinated I‐QTP‐4F) by attaching different halogens into 2D‐conjugation extended dibenzo[f,h]quinoxaline core are developed. Among these X‐QTP‐4F, Cl‐QTP‐4F has a higher absorption coefficient, optimized molecular crystallinity and packing, suitable cascade energy levels, and complementary absorption with PM6:L8‐BO host. Moreover, among ternary PM6:L8‐BO:X‐QTP‐4F blends, PM6:L8‐BO:Cl‐QTP‐4F obtains a more uniform and size‐suitable fibrillary network morphology, improved molecular crystallinity and packing, as well as optimized vertical phase distribution, thus boosting charge generation, transport, extraction, and suppressing energy loss of OSCs. Consequently, the PM6:L8‐BO:Cl‐QTP‐4F‐based OSCs achieve a 19.0% efficiency, which is among the state‐of‐the‐art OSCs based on 2D‐conjugated Y‐SMAs and superior to these devices based on PM6:L8‐BO host (17.70%) and with guests of H‐QTP‐4F (18.23%), Br‐QTP‐4F (18.39%), and I‐QTP‐4F (17.62%). The work indicates that halogenation in 2D‐structured dibenzo[f,h]quinoxaline core of Y‐SMAs guests is a promising strategy to gain efficient ternary OSCs. [ABSTRACT FROM AUTHOR]

Photosynthesis, essential for life on earth, sustains diverse processes by providing nutrition in plants and microorganisms. Especially, photosynthesis is increasingly applied in disease treatments, but its efficacy is substantially limited by the well‐known low penetration depth of external light. Here, ultrasound‐mediated photosynthesis is reported for enhanced sonodynamic tumor therapy using organic sonoafterglow (ultrasound‐induced afterglow) nanoparticles combined with cyanobacteria, demonstrating the proof‐of‐concept sonosynthesis (sonoafterglow‐induced photosynthesis) in cancer therapy. Chlorin e6, a typical small‐molecule chlorine, is formulated into nanoparticles to stimulate cyanobacteria for sonosynthesis, which serves three roles, i.e., overcoming the tissue‐penetration limitations of external light sources, reducing hypoxia, and acting as a sonosensitizer for in vivo tumor suppression. Furthermore, sonosynthetic oxygenation suppresses the expression of hypoxia‐inducible factor 1α, leading to reduced stability of downstream SLC7A11 mRNA, which results in glutathione depletion and inactivation of glutathione peroxidase 4, thereby inducing ferroptosis of cancer cells. This study not only broadens the scope of microbial nanomedicine but also offers a distinct direction for sonosynthesis. [ABSTRACT FROM AUTHOR]

The replacement of a CC unit with an isoelectronic BN unit in aromatic systems can give rise to molecules and materials with fascinating properties. We report here the synthesis, characterization, and reactivity of a 1,4,2,3‐diazadiborole species, 2, featuring an unprecedented 6π‐aromatic BN‐heterocyclic moiety that is isoelectronic to cyclopentadienide (Cp−). Bearing an unsymmetrical B=B entity, 2 exhibits reactivity toward oxidants, protic reagents, electrophiles, and unsaturated substrates. This reactivity facilitates the synthesis of a variety of novel mono‐ and bicyclic organoboron derivatives through mechanisms including ring retention, cleavage/recombination, annulation, and expansion. These findings reveal innovative synthetic routes to BN‐embedded aromatic compounds via desymmetrization, affording unique building blocks for synthetic chemistry. [ABSTRACT FROM AUTHOR]

This study aimed to establish a novel noninvasive model based on the serum N‐glycan spectrum for providing an objective value for determining the stage of liver necroinflammation related to chronic hepatitis B (CHB) patients. N‐glycan profiles of the sera of 295 treatment‐naïve CHB patients were analyzed. N‐glycan profiles were tested for different liver necroinflammation stages using DNA sequence‐assisted fluorophore‐assisted carbohydrate electrophoresis. A serum N‐glycan model named N‐glycan‐LI (NGLI) using support vector machine was selected to evaluate the classification of liver necroinflammation (G < 2 and G ≥ 2). The area under the receiver operating characteristic curves (AUROCs) was 0.898 (training set, n = 236) and 0.911 (validation set, n = 59) regardless of the stage of liver fibrosis (AUROC = 0.886 and 0.926, respectively, in S < 2 and S ≥ 2 group). The NGLI correspondingly had the highest specificity (SP) of 90.79% and negative predictive value of 92.00% in an inactive stage (including immune‐tolerant [IT] and inactive‐carrier [IC] stage), had the highest positive predictive value of 95.18% in stage immune‐active, and had the highest SP of 93.94% in grey zone IT + IC. N‐glycan profiles appear to correlate well with hepatic necroinflammation in CHB when compared with liver biopsy. The newly developed model appears to reliably predict liver damage in naïve‐treatment patients with CHB. [ABSTRACT FROM AUTHOR]

White adipose tissue accumulation and inflammation contribute to obesity by inducing insulin resistance. Herein, we aimed to screen the synergistic components of the herbal pair Coptidis Rhizoma‐Glycyrrhizae Radix et Rhizoma for the treatment of insulin resistance and explore the potential synergistic mechanisms. Enzyme‐linked immunosorbent assay and quantitative PCR were used to detect expression levels of inflammatory genes in vitro and in vivo. Western blotting and immunohistochemistry were performed to detect protein levels of the insulin signaling pathway and macrophage markers. The effects on obesity‐induced insulin resistance were verified using a diet‐induced obesity (DIO) mouse model. Interactions between macrophage and adipocyte were assessed using a cellular supernatant transfer assay. Berberine (BBR) and isoliquiritigenin (ISL) alleviated mRNA levels and secretion of inflammatory genes in vitro and in vivo. Furthermore, BBR acted synergistically with ISL to ameliorate obesity and dyslipidemia in DIO mice. Meanwhile, the combination treatment significantly improved glucose intolerance and insulin resistance and decreased M1‐macrophage accumulation and infiltration in the adipose tissue. Mechanistically, co‐treatment with BBR and ISL upregulated the protein expression of the IRS1‐PI3K‐Akt insulin signaling pathway, enhanced glucose uptake in adipocyte, and suppressed the interaction between macrophage and adipocyte. BBR and ISL were identified as the synergistic components of the herbal pair Coptidis Rhizoma‐Glycyrrhizae Radix et Rhizoma for treating insulin resistance. The synergistic combination of BBR with ISL can be a promising and effective strategy for improving obesity‐induced adipose inflammation and insulin resistance. [ABSTRACT FROM AUTHOR]

Introduction: The seeds of Sterculia lychnophora Hance, commonly known as Pangdahai (PDH) in Chinese, have found extensive use in both culinary and traditional medicinal practices. However, a comprehensive understanding of the chemical composition of PDH has been lacking. Objectives: This study proposes a strategy that integrates biosynthetic pathway analysis with feature‐based molecular networking (FBMN), aiming for a thorough and global characterization of the chemical compositions of PDH. Methodology: The FBMN map reveals potential compounds with structural similarity, and the MS/MS fragments could be annotated based on library matches, which could predict the plausible biosynthetic pathways in PDH, accomplishing the annotation of compounds clustered in FBMN by integrating biosynthetic pathways. Results: Consequently, 126 compounds were plausibly or unambiguously identified, including 37 phenolic acids and glycosides, 20 flavonoids and glycosides, 12 procyanidins, 21 alkaloids, 22 lipids, and 14 others. Leveraging the information, 40 compounds, including 1 unique isoquinoline alkaloid and 2 rare linear furocoumarins, were isolated and confirmed. Conclusions: This study not only demonstrates a highly effective approach for identifying compounds within complex herbal mixtures but also establishes a robust foundation for the further development of PDH. A novel strategy integrated biosynthetic pathway analysis and with FBMN was developed. The first comprehensive investigation of the secondary metabolites in PDH. The doub‐caffeoyl‐glucosides, phenolamides, procyanidins, isoquinoline alkaloids and phospholipids were reported in PDH for the first time. Isoquinoline alkaloid and linear furocoumarins were isolated from PDH for the first time. [ABSTRACT FROM AUTHOR]

The efficient removal of low‐concentration endocrine disruptors is crucial for the protection of the aquatic environment. In this study, porous polymer adsorbent materials were modified by nanosecond pulsed discharge plasma to achieve efficient adsorption of low‐concentration bisphenol A (BPA). The removal efficiency of BPA reached 99% after 10 min of plasma modification at a pulse peak voltage of 28 kV, which increased by 25.8% compared to the raw materials. This enhancement was attributed to the increase of active sites and oxygen‐containing functional groups. The adsorption behaviors of the porous polymer materials were primarily dominated by monolayer chemisorption. Subsequently, comparative experiments further verified the high‐efficiency adsorption performance of porous polymer materials after plasma treatment. [ABSTRACT FROM AUTHOR]

Background: Tocilizumab is commonly used for the management of chimeric antigen receptor (CAR) T‐cell therapy–associated cytokine release syndrome (CRS). However, it remains unknown whether tocilizumab or its dosage affects the efficacy and safety of CAR T‐cell therapy. The objective of this multicenter retrospective study was to explore the impact of tocilizumab on CAR T‐cell therapy. Methods: In total, 93 patients with B‐cell acute lymphoblastic leukemia (B‐ALL) receiving humanized anti‐CD19 CAR T cells were recruited from May 2016 to November 2022. Forty‐five patients received tocilizumab (tocilizumab group), whereas 48 patients did not (nontocilizumab group). Thirteen patients received >1 dose of tocilizumab. The primary end point was the effect of tocilizumab on the efficacy and safety of CAR T cells. Additionally, proliferation, killing, and cytokine assays of CAR T cells were performed in vitro in the presence of tocilizumab. Results: The median age of the patients was 33 years, with 47 males and 46 females. Patients in the tocilizumab group showed similar complete response (CR) rate, overall survival (OS), and event‐free survival (EFS) compared with the nontocilizumab group. Compared with patients who received ≤1 dose of tocilizumab, receiving >1 dose of tocilizumab did not affect their CR rate, OS, or EFS. In the tocilizumab group, all patients experienced CRS and 26.7% experienced immune effector cell–associated neurotoxicity syndrome (ICANS). In the nontocilizumab group, 64.6% of patients experienced CRS and 8.3% experienced ICANS. Up to 75% of ICANS and 87.5% of grade ≥3 ICANS occurred in the tocilizumab group. In vitro, tocilizumab did not impair the proliferation and killing effects of CAR T cells. Conclusions: Tocilizumab does not affect the efficacy of CAR T cells but may increase the likelihood of ICANS. Tocilizumab does not affect the efficacy of anti‐CD19 chimeric antigen receptor (CAR) T cells and the survival outcome of patients with B‐cell acute lymphoblastic leukemia. Tocilizumab may increase the likelihood of immune effector cell–associated neurotoxicity syndrome after CAR T‐cell therapy. [ABSTRACT FROM AUTHOR]

Lithium‐sulfur (Li‐S) battery shows promising development potential in secondary lithium‐ion batteries. However, the shuttle effect of polysulfides, uncontrollable lithium dendrite growth, and safety hazards in conventional liquid electrolytes limit the popularity of Li‐S batteries in the future commercial market. In this work, a high‐performance gel electrolyte (GPE) was prepared in situ by initiating the ring‐opening polymerization of 1,3‐dioxolane (DOL) with aluminum trifluoromethanesulfonate (Al(OTf)3) and using diethylene glycol dimethyl ether (DME) as a plasticizer, which can effectively improve the interfacial compatibility between sulfur cathode and the electrolyte, as well as the stability of lithium anode. The electrochemical performance of the poly‐DOL (PDOL) GPE was optimized by adjusting the concentration ratio of the initiator. When the concentration of Al(OTf)3 is 4 mM, the PDOL GPE has a high ionic conductivity up to 3.81 × 10−4 S cm−1 and a lithium ion migration number of 0.57. The assembled quasi‐solid‐state Li‐S batteries shows an initial discharge specific capacity of 908.1 mAh g−1 at 0.1 C with a capacity retention of 68% after 240 cycles, and its average Coulombic efficiency is maintained at 96.1%. This gel electrolyte design provides a feasible practical idea in quasi‐solid‐state Li‐S batteries. [ABSTRACT FROM AUTHOR]

The sustainable development of novel photo/electrocatalytic CO2/N2 fixation for chemical synthesis is predicated on reliable, accurate, and rapid detection methods. The directness, specificity, and simultaneity in detecting multiple molecules of the 1H nuclear magnetic resonance (1H‐NMR) technique have aroused increasing interest in photo/electrocatalysis. Thus far, two data processing means have been developed for the precise 1H‐NMR data processing: peak integral and peak height methods. However, few detailed studies offer a clear steer for choosing data processing methods for the concerned products in photo/electrocatalysis, especially the guidelines under the conditions of baseline distortions induced by water suppression. Herein, the feasible practices are restudied to quantify classical products in photo/electrocatalytic CO2/N2 fixation. On the basis of experimental results, 1H‐NMR data processing methods (peak integral and peak height methods) are found to convey different applicability for the different low‐concentration products, while introducing water suppression in the 1H‐NMR tests. The essential reason can be attributed to the baseline distortions caused by the water suppression, which arouses differentiated deviation of peaks with different peak widths. With this in mind, an accessible quantification criterion is provided to avoid superfluous input of time or cost in precise 1H‐NMR detection of low‐concentration products. [ABSTRACT FROM AUTHOR]

A transition‐metal‐free protocol is proposed for the selective oxidation of flavones, providing various sulfoxide/sulfone‐flavonoids in excellent yields. This strategy features excellent selectivities, high yields and broad substrate scope. The combination of oxone (2KHSO5 ⋅ KHSO 4⋅ K2SO4) as the sole oxidant and NaHCO3/Na2CO3 as the buffer play an important role in the process, in which the amounts of oxone and reaction temperatures are the key to the outstanding selectivities and high efficiency of the reaction. It should be noteworthy that a class of novel sulfone‐flavonols is also synthesized through triple oxidation. Moreover, the glycosylation of sulfone‐flavonols has been realized. [ABSTRACT FROM AUTHOR]

In this study, we isolated human periodontal ligament cells (hPDLCs) to find the optimal time of LIPUS stimulation and to explore how LIPUS affects inflammatory and osteogenic responses in hPDLCs in an inflammatory environment. The target molecules of LIPUS were identified by high‐throughput sequencing. RT–qPCR and WB were used to detect how LIPUS affected the expression of related genes in TNFα‐induced inflammation. The expression of ROS and inflammatory factors was detected by flow cytometry. Immunohistochemistry was used to further verify gene expression in rats. hPDLCs were isolated successfully. The optimal LIPUS stimulation condition was 45 mW/cm2 for 30 min and continued for 3 days, and this intensity significantly promoted the osteogenesis and mineralization of hPDLCs. LIPUS significantly inhibited the upregulation of IL‐6 and ROS, increased the percentage of cells in the G2 phase, inhibited cell apoptosis, and inhibited the upregulation of TLR5 expression in an inflammatory environment. LIPUS can effectively restrain the inflammation and oxidative stress response of hPDLCs and promote osteogenesis in an inflammatory environment. LIPUS inhibited the periodontal inflammatory response through TLR5 in hPDLCs and dental pulp. [ABSTRACT FROM AUTHOR]

Consider Dirichlet problems of Laplace's equation in a bounded simply‐connected domain S$$ S $$, and use the null field equation (NFE) of Green's representation formulation, where the source nodes Q$$ Q $$ are located on a pseudo‐boundary ΓR$$ {\Gamma}_R $$ outside S$$ S $$ but not close to its boundary Γ(=∂S)$$ \Gamma \kern0.3em \left(=\partial S\right) $$. Simple algorithms are proposed in this article by using the central rule for the NFE, and the normal derivatives uν$$ {u}_{\nu } $$ of the solutions on the boundary Γ(=∂S)$$ \Gamma \kern0.3em \left(=\partial S\right) $$ can be easily obtained. These algorithms are called the discrete null field equation method (DNFEM) because the collocation equations are, indeed, the direct discrete form of the NFE. The bounds of the condition number are like those by the method of fundamental solutions (MFS) yielding the exponential growth as the number of unknowns increases. One trouble of the DNFEM is the near singularity of integrations for the solutions in boundary layers in Green's representation formulation. The traditional BEM also suffers from the same trouble. To deal with the near singularity, quadrature by expansions and the sinh transformation are often used. To handle this trouble, however, we develop two kinds of new techniques: (I) the interpolation techniques by Taylor's formulas with piecewise q$$ q $$‐degree polynomials and the Fourier series, and (II) the mini‐rules of integrals, such as the mini‐Simpson's and the mini‐Gaussian rules. Error analysis is made for technique I to achieve optimal convergence rates. Numerical experiments are carried out for disk domains to support the theoretical analysis made. The numerical performance of the DNFEM is excellent for disk domains to compete with the MFS. The errors with O(10−4)$$ O\left(1{0}^{-4}\right) $$ can be obtained by combination algorithms, which are satisfactory for most engineering problems. In summary, the new simple DNFEM is based on the NFE, which is different from the boundary element method (BEM). The theoretical basis in error and stability has been established in this article. One trouble in seeking the numerical solutions in boundary layers has been handled well; this is also an important contribution to the BEM. Besides, numerical experiments are encouraging. Hence the DNFEM is promising, and it may become a new boundary method for scientific/engineering computing. [ABSTRACT FROM AUTHOR]

Background: People with severe asthma remain at risk of toxicity from maintenance oral corticosteroid (OCS) use and/or frequent OCS burst therapy. Cumulative exposures above 500–1000 mg prednisolone are associated with adverse effects, and recently OCS stewardship principles were promulgated to guide OCS prescription. Aims: To examine real‐world registry data to quantify OCS burden, ascertain trends over time in prescription and assess whether opportunities to implement steroid‐sparing strategies were utilised. Methods: Participants were enrolled in the Australasian Severe Asthma Registry for the period 2013–2021. Assessments were taken at enrolment and then annual follow‐up, which included asthma control and OCS use. Descriptive analyses were performed, and subgroups were compared at baseline and over time. Results: Nine hundred and twenty‐four participants were evaluated and 215/924 (23%) were taking maintenance OCS at baseline, with 44% and 32% of participants having exposure to ≥500 or 1000 mg of OCS respectively in the prior year. Twelve months later, an additional 10% and 9% of participants reached cumulative doses of 500 or 1000 mg. People exceeding thresholds had ongoing poor asthma control. At baseline, 240/924 (26%) people were treated with asthma biological therapy. An additional 83 (12%) participants were identified as potentially benefiting from this steroid‐sparing medication. Of these patients, only 23% commenced a biologic agent in the next 12 months. Conclusions: A large national asthma registry identifies exposure to toxic cumulative doses of OCS in more than a third of participants, with further subsequent cumulative dose escalation over 2 years. Steroid‐sparing strategies were often not employed, highlighting the need for implementation of OCS stewardship initiatives. [ABSTRACT FROM AUTHOR]

Hairy tofu is a famous Chinese snack that is made from soybeans and rich in various nutrients. In order to further explore the antioxidant peptides of hairy tofu hydrolysates, seven proteases were used to hydrolyze hairy tofu. The results of in vitro radical scavenging activity showed that hairy tofu hydrolysates obtained by pancreatin exhibited the highest antioxidant activity. After Sephadex G‐25 gel filtration and reversed‐phase high‐performance liquid chromatography (RP‐HPLC), 97 peptides were identified in the most antioxidant fraction using liquid chromatography‐mass spectrometry/mass spectrometry (LC–MS/MS). Among them, nine peptides were synthesized and their antioxidant activities were assessed using a H2O2‐induced oxidative 293T cell model. Finally, four peptides (QCESHK, LAWNEGR, NLQGENEWDQK, and FTEMWR) at concentrations of < 50 μg/ml significantly decreased the malondialdehyde content compared with the model group, displaying in vivo antioxidant activity and low cytotoxicity. Overall, this research provided the choice of using hairy tofu peptides as antioxidant products in the pharmaceutical and food industries. [ABSTRACT FROM AUTHOR]

This document is an introduction to a collection of letters discussing various themes and topics in cognitive science. The letters cover a range of subjects, including pragmatic explanations, grammatical systems, consciousness, social dimensions of cognition, diversity in cognitive science, core aspects of cognition, language and learning, high-level cognition, technology and cognitive science, and more. The document emphasizes the importance of empirical and theoretical substance in the field of cognitive science and invites readers to engage in lively discussion and collaboration. [Extracted from the article]

Main Problem: Anhedonia is a critical diagnostic symptom of major depressive disorder (MDD), being associated with poor prognosis. Understanding the neural mechanisms underlying anhedonia is of great significance for individuals with MDD, and it encourages the search for objective indicators that can reliably identify anhedonia. Methods: A predictive model used connectome‐based predictive modeling (CPM) for anhedonia symptoms was developed by utilizing pre‐treatment functional connectivity (FC) data from 59 patients with MDD. Node‐based FC analysis was employed to compare differences in FC patterns between melancholic and non‐melancholic MDD patients. The support vector machines (SVM) method was then applied for classifying these two subtypes of MDD patients. Results: CPM could successfully predict anhedonia symptoms in MDD patients (positive network: r = 0.4719, p < 0.0020, mean squared error = 23.5125, 5000 iterations). Compared to non‐melancholic MDD patients, melancholic MDD patients showed decreased FC between the left cingulate gyrus and the right parahippocampus gyrus (p_bonferroni = 0.0303). This distinct FC pattern effectively discriminated between melancholic and non‐melancholic MDD patients, achieving a sensitivity of 93.54%, specificity of 67.86%, and an overall accuracy of 81.36% using the SVM method. Conclusions: This study successfully established a network model for predicting anhedonia symptoms in MDD based on FC, as well as a classification model to differentiate between melancholic and non‐melancholic MDD patients. These findings provide guidance for clinical treatment. [ABSTRACT FROM AUTHOR]

Purpose: Uterine fibroids (UF) are the most frequent tumors in ladies and can pose an enormous threat to complications, such as miscarriage. The accuracy of prognosis may also be affected by way of doctor inexperience and fatigue, underscoring the want for automatic classification fashions that can analyze UF from a giant wide variety of images. Methods: A hybrid model has been proposed that combines the MobileNetV2 community and deep convolutional generative adversarial networks (DCGAN) into useful resources for medical practitioners in figuring out UF and evaluating its characteristics. Real‐time automated classification of UF can aid in diagnosing the circumstance and minimizing subjective errors. The DCGAN science is utilized for superior statistics augmentation to create first‐rate UF images, which are labeled into UF and non‐uterine‐fibroid (NUF) classes. The MobileNetV2 model then precisely classifies the photos based totally on this data. Results: The overall performance of the hybrid model contrasts with different models. The hybrid model achieves a real‐time classification velocity of 40 frames per second (FPS), an accuracy of 97.45%, and an F1 rating of 0.9741. Conclusion: By using this deep learning hybrid approach, we address the shortcomings of the current classification methods of uterine fibroid. [ABSTRACT FROM AUTHOR]

Tilletia horrida is an important soilborne fungal pathogen that causes rice kernel smut worldwide. We found a glycoside hydrolase family 128 protein, designated ThGhd_7, caused cell death in Nicotiana benthamiana leaves. The predicted signal peptide (SP) of ThGhd_7 targets it for secretion. However, loss of the SP did not affect its ability to induce cell death. The 23–201 amino acid sequence of ThGhd_7 was sufficient to trigger cell death in N. benthamiana. ThGhd_7 expression was induced and upregulated during T. horrida infection. ThGhd_7 localised to both the cytoplasm and nucleus of plant cells, and nuclear localisation was required to induce cell death. The ability of ThGhd_7 to trigger cell death in N. benthamiana depends on RAR1 (required for Mla12 resistance), SGT1 (suppressor of G2 allele of Skp1), and BAK1/SERK3 (somatic embryogenesis receptor‐like kinase 3). Heterologous overexpression of ThGhd_7 in rice reduced reactive oxygen species (ROS) production and enhanced susceptibility to T. horrida. Further research revealed that ThGhd_7 interacted with and destabilised OsSGT1, which is required for ROS production and is a positive regulator of rice resistance to T. horrida. Taken together, these findings suggest that T. horrida employs ThGhd_7 to disrupt ROS production and thereby promote infection. Summary Statement: Tilletia horrida is an important soilborne fungal pathogen that causes rice kernel smut (RKS) worldwide. This article finds that glycoside hydrolase family 128 protein ThGhd_7 suppressed host immune responses and thereby promoted T. horrida infection by modulating OsSGT1‐mediated reactive oxygen species (ROS) production. [ABSTRACT FROM AUTHOR]

Emerging evidence suggests differential antagonism of lactic acid‐producing bacteria (LAB) to Helicobacter pylori, posing challenges to human health and food safety due to unclear mechanisms. This study assessed 21 LAB strains from various sources on H. pylori growth, urease activity, and coaggregation. Composite scoring revealed that Latilactobacillus sakei LZ217, derived from fresh milk, demonstrates strong inhibitory effects on both H. pylori growth and urease activity. L. sakei LZ217 significantly reduced H. pylori adherence of gastric cells in vitro, with inhibition ratios of 47.62%. Furthermore, in vivo results showed that L. sakei LZ217 alleviated H. pylori‐induced gastric mucosa damage and inflammation in mice. Metabolomic exploration revealed metabolic perturbations in H. pylori induced by L. sakei LZ217, including reduced amino acid levels (e.g., isoleucine, leucine, glutamate, aspartate, and phenylalanine) and impaired carbohydrate and nucleotide synthesis, contributing to the suppression of ureA (28.30%), ureE (84.88%), and ureF (59.59%) expressions in H. pylori. This study underscores the efficacy of LAB against H. pylori and highlights metabolic pathways as promising targets for future interventions against H. pylori growth and colonization. [ABSTRACT FROM AUTHOR]

Seed germination and dormancy represent critical phases in the life cycle of plants, tightly regulated by endogenous phytochrome levels and environment signals. High temperatures (HT) induce the overaccumulation of reactive oxygen species (ROS) and increase abscisic acid (ABA), thereby inhibiting seed germination. Our previous findings showed that HT induced the burst of reactive nitrogen species (RNS), increasing the S‐nitrosylation modification of HFR1, which effectively blocks seed germination. Importantly, stabilizing HFR1 has been shown to significantly mitigate the inhibitory effect of HT on seed germination. In this study, we reported that HT increased the protein abundance of ABI4, a crucial component in ABA signaling, which in turn activates the expression of RbohD while suppressing the expression of VTC2. This leads to the rapid generation of ROS, thereby inhibiting seed germination. Consistently, the seed germination of abi4 mutant showed insensitivity to HT with lower ROS level during seed germination, whereas transgenic lines overexpressing ABI4 showed reduced germination rates accompanied by elevated ROS levels. Furthermore, we noted that HFR1 interacts with ABI4 to sequester its activity under normal conditions. However, HT‐induced ROS triggered the degradation of HFR1, consequently releasing ABI4 activity. This activation of ABI4 promotes RbohD expression, culminating in a ROS burst that suppresses seed germination. Thus, our study unveils a novel function for ABI4 in regulating ROS level and seed germination under HT stress. Throughout this process, HFR1 plays a critical role in restraining ABI4 activity to maintain an optimal endogenous ROS level, thereby ensuring seed germination under favorable environmental conditions. [ABSTRACT FROM AUTHOR]

This study develops a Bayesian method to analyze optimal burn‐in policy for heterogeneous components with minimal repair. We use the non‐homogeneous Poisson processes with different power law intensity functions to model the minimal repair processes for heterogeneous components. Since the component from the weak subpopulation may fail more frequently, the total number of minimal repairs can be used for establishing a screening rule. By screening, we can decide whether the component after burn‐in should be eliminated or not. Considering the uncertainty of model parameters, we generate a minimally repaired data set of components by simulation. Then, we obtain the model parameters estimators by using Bayesian method combined with the existing data. We further analyze and get the optimal burn‐in settings under cost and performance optimization model. A numerical example is used to verify the effectiveness of the Bayesian method. [ABSTRACT FROM AUTHOR]

Nickel‐catalyzed transannulation reactions triggered by the extrusion of small gaseous molecules have emerged as a powerful strategy for the efficient construction of heterocyclic compounds. However, their use in asymmetric synthesis remains challenging because of the difficulty in controlling stereo‐ and regioselectivity. Herein, we report the first nickel‐catalyzed asymmetric synthesis of N−N atropisomers by the denitrogenative transannulation of benzotriazones with alkynes. A broad range of N−N atropisomers was obtained with excellent regio‐ and enantioselectivity under mild conditions. Moreover, density functional theory (DFT) calculations provided insights into the nickel‐catalyzed reaction mechanism and enantioselectivity control. [ABSTRACT FROM AUTHOR]

The parent‐child relationship plays an important role in shaping adolescents' mental health during the COVID‐19 pandemic. However, the mechanisms underlying the association between the parent‐child relationship and mental health are unclear. Using a 2‐wave longitudinal design, this study examined the role of both mother‐child and father‐child relationships during home quarantine in boarding school students' internalizing and externalizing problems after school reopening, and the mediating roles of academic buoyancy and academic engagement. A total of 1967 boarding high school students completed a battery of self‐report questionnaires before and after school reopening. Results indicated that both father‐child and mother‐child relationships indirectly contributed to internalizing and externalizing problems through the interlinked mediation path of academic buoyancy and academic engagement. The mother‐child relationship had greater influence on internalizing and externalizing problems than the father‐child relationship. These findings clarify the associations between the parent‐child relationships and mental health problems of boarding high school students during the transition to school reopening in the COVID‐19 pandemic, expanding our understanding of psychological adjustment related to parent‐child relationships and the potential mechanisms of these relationships. Practitioner Points: Parent‐child relationship positively predicted boarding school students' academic buoyancy and academic engagement.Boarding school students' academic buoyancy and academic engagement sequentially mediated the relationship between parent‐child relationship and internalizing and externalizing problems.Mother‐child relationship had more influence on internalizing and externalizing problems than the father‐child relationship. [ABSTRACT FROM AUTHOR]

Aims: Existing research indicates that patients with heart failure (HF) may have restricted access to guideline‐directed medical therapy (GDMT) when their blood pressure (BP) is comparatively low. However, recent clinical trials suggest that HF patients with low BP could still benefit from certain HF medications, which have a minimal impact on BP. This systematic review and meta‐analysis was conducted to determine whether this applies to all GDMT. Methods and results: A systematic search of MEDLINE and EMBASE was conducted for studies published from inception to 10 January 2024. Randomized controlled trials were selected if they reported on the longitudinal change of systolic BP (SBP) due to GDMT, or the risks of cardiovascular events in HF patients based on SBP categories. Weighted mean difference (WMD), hazard ratio or relative risk, and corresponding 95% confidence intervals (CI) were pooled for meta‐analysis where possible. Data from 20 studies, encompassing information on 84 782 individuals, were analysed. Overall, GDMT is associated with lower SBP (WMD, −2.16; 95% CI −2.86 to −1.46), with no significant difference between baseline low and non‐low BP subgroups (interaction p = 0.810). However, SBP of the treatment group increased by 5.8 mmHg from baseline in the low SBP subgroup during follow‐up, while it decreased by 4.0 mmHg in the baseline non‐low SBP subgroup. GDMT demonstrated similar cardiovascular benefits and risk of hypotension between low and non‐low SBP subgroups (interaction p = 0.318 and 0.903, respectively). Conclusions: Guideline‐directed medical therapy is associated with a negligible decrease in SBP, but can provide similar cardiovascular benefits in both low and non‐low SBP HF patients, with no significant interaction with SBP as to hypotension. Therefore, GDMT should be initiated and maintained in HF patients with low BP. [ABSTRACT FROM AUTHOR]

Synergistic changes between tumor‐associated macrophages (TAMs) and cancer‐associated fibroblasts (CAFs) aggravated immune evasion of hepatocellular carcinoma (HCC), however, the underlying molecular mechanisms remain elusive. Their continuous and dynamic interactions are subject to bioactive molecule changes. A real‐time and in situ monitoring method suitable for in vivo research of these processes would be indispensable but is scarce. In this study, a dual imaging strategy that tracing the TAMs and CAFs simultaneously was developed using a new arginase‐specific probe and established CAFs‐specific probe. The emerging roles of arginase in mediating CAFs activation in mice were explored. Results showed arginase up‐regulation in TAMs, followed by proline increase. Subsequently, proline produced by TAMs initiated the activation of CAFs. Through the JAK‐STAT signaling, CAFs up‐regulated the PD‐L1 and CTLA‐4, ultimately promoting immune evasion of HCC. This study revealed a new mechanism by which TAMs and CAFs collaborate in immune evasion, providing new targets for HCC immunotherapy. [ABSTRACT FROM AUTHOR]

Background and Aims: Accurate preoperative prediction of microvascular invasion (MVI) and recurrence‐free survival (RFS) is vital for personalised hepatocellular carcinoma (HCC) management. We developed a multitask deep learning model to predict MVI and RFS using preoperative MRI scans. Methods: Utilising a retrospective dataset of 725 HCC patients from seven institutions, we developed and validated a multitask deep learning model focused on predicting MVI and RFS. The model employs a transformer architecture to extract critical features from preoperative MRI scans. It was trained on a set of 234 patients and internally validated on a set of 58 patients. External validation was performed using three independent sets (n = 212, 111, 110). Results: The multitask deep learning model yielded high MVI prediction accuracy, with AUC values of 0.918 for the training set and 0.800 for the internal test set. In external test sets, AUC values were 0.837, 0.815 and 0.800. Radiologists' sensitivity and inter‐rater agreement for MVI prediction improved significantly when integrated with the model. For RFS, the model achieved C‐index values of 0.763 in the training set and ranged between 0.628 and 0.728 in external test sets. Notably, PA‐TACE improved RFS only in patients predicted to have high MVI risk and low survival scores (p <.001). Conclusions: Our deep learning model allows accurate MVI and survival prediction in HCC patients. Prospective studies are warranted to assess the clinical utility of this model in guiding personalised treatment in conjunction with clinical criteria. [ABSTRACT FROM AUTHOR]