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Ethnopharmacological Relevance: Zangsiwei(ZSW) is a traditional Tibetan medicine from China consisting of extracts of Rhododendron anthopogonoides Maxim, Gentiana Tourn, Corydalis hendersonii Hemsl and Berberis kansuensis C.K.Schneid. Traditionally, ZSW has been used by Tibetan physicians to treat chronic respiratory diseases. The role of ZSW in particulate matter-induced lung inflammation and fibrosis remains unclear., Aim of the Study: Combining non-targeted metabolomics, network pharmacology, and molecular docking to explore the mechanism of ZSW in the treatment of particulate matter-induced lung inflammation and fibrosis, and validated by in vivo and in vitro experiments., Materials and Methods: The serum metabolite profile post-ZSW administration was first identified utilizing non-targeted metabolomics. Network pharmacology and molecular docking were employed to predict potential bioactive components and their corresponding targets. The in silico predictions were subsequently validated through in vivo studies in mice exposed to PM2.5 and silica dust, as well as in vitro studies utilizing human lung epithelial cells (A549) and lung fibroblasts (MRC5)., Results: Metabolomic analysis identified specific serum metabolites that were associated with ZSW treatment. Network pharmacology and molecular docking identified key targets involved in the Transforming growth factor-β (TGF-β)/SMAD pathway, which were subsequently validated through in vivo experiments demonstrating a reduction in lung inflammation and fibrosis in ZSW-treated mice. In vitro studies demonstrated that ZSW exerts protective effects against PM2.5-induced cytotoxicity and modulates fibrotic markers in a dose-dependent manner. This is consistent with the inhibition of the TGF-β/SMAD pathway., Conclusion: Our integrated approach, which combines non-targeted metabolomics, network pharmacology, and molecular docking, followed by rigorous in vivo and in vitro validation, establishes ZSW as a potential therapeutic agent for particulate matter-induced lung inflammation and fibrosis., 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.)

Skin, as the first line of defence of the human body, is exposed to dangers such as overheating substances, ultraviolet rays, and environmental pollutants, and the incidence of skin diseases is increasing annually. Oxidative stress plays a dominant role in most skin diseases. Abelmoschus manihot (L.) medic flower (TEA) is a traditional Chinese medicine widely used to treat injuries to the skin such as water and fire scalds. It has been reported that TEA has excellent antioxidant effects. In this study, we aimed to explore the antioxidant and mitochondrial protection effects of TEA in H 2 O 2 -mediated HaCaT cell damage. HaCaT cells were incubated with H 2 O 2 to simulate oxidative stress in the skin. The effect of TEA on HaCaT cells was also evaluated. Cell morphology was observed via inverted microscopy, and cell viability was measured via the MTT reagent. The cells were stained with Hoechst 33,324 solution. Reactive oxygen species (ROS), superoxide dismutase (SOD), malondialdehyde (MDA) and ATP detection kits were used to detect the corresponding indicators. The mitochondrial membrane potential was detected by JC-1. RT-PCR was used to detect mRNA and mtDNA expression. The expression of the target protein was detected by Western blotting and immunofluorescence. H 2 O 2 triggered oxidative damage in HaCaT cells, which manifested as apoptosis, increased ROS and MDA contents, and decreased SOD activity. H 2 O 2 activates the KEAP1/Nrf2/NQO1 signalling pathway, which decreases the expression of the intracellular KEAP1 protein and slightly increases the expression of the Nrf2 and NQO1 proteins, further causing mitochondrial oxidative stress, resulting in changes in the mitochondrial membrane potential, a reduction in the mtDNA copy number, and decreased expression of the PGC-1α and TFAM proteins. In addition the expression of mitochondrial respiratory chain genes and proteins decreased. TEA promoted the expression of Nrf2 in HaCaT cells, activated the downstream antioxidant response, and alleviated the oxidative stress and mitochondrial damage caused by H 2 O 2 . ML385 is an Nrf2 inhibitor, under which the antioxidant and mitochondrial protective effects of TEA are inhibited. When TFAM was knocked down, the protective effect of TEA on mitochondria was also inhibited. TEA protects HaCaT cells from H 2 O 2 -induced oxidative damage and mitochondrial oxidative damage through the KEAP1/Nrf2/NQO1/PGC-1α/TFAM pathway., Competing Interests: Declarations. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Background: Displaced tibial tubercle (TT) fractures in adolescents are typically treated with open reduction and internal fixation. While metallic screw (MS) fixation provides strong stability, it often results in a high incidence of postoperative screw head protrusion or irritation, leading to additional removal surgery. Bioabsorbable screw (BS) fixation presents an alternative that may avoid these issues, though its stability has not yet been extensively documented in the literature. This study aims to compare the efficacy of BS versus MS in the fixation of TT fractures., Methods: A retrospective analysis was conducted on adolescent patients with TT fractures who underwent surgical treatment from September 2015 to September 2023. Patients were divided into two groups based on the fixation method: The BS group and the MS group. Data collected included patient demographics, fracture details, treatment strategies, radiological and clinical rehabilitation outcomes, and postoperative complications. Knee joint function was evaluated using the Lysholm and Tegner scores. Statistical analysis was performed to identify differences between the variables of the two groups., Results: A total of 30 patients with 32 fractures were included, with 15 fractures in the BS group and 17 in the MS group. The average follow-up period was 42.1 (range: 12.0-109.5) months. The demographic characteristics, fracture details, and treatment strategies were comparable between the two groups. No significant differences were observed between the groups in fracture healing time, time to return to pre-injury activities, or knee joint function as assessed by the Lysholm and Tegner scores at the final follow-up. However, compared with the MS group, the BS group showed a shorter time to regain full range of motion (ROM) in the knee joint and experienced lower rates of postoperative hardware irritation and joint stiffness., Conclusions: Both BS and MS fixations are safe and effective for treating adolescent TT fractures. BS fixation has the advantages of avoiding hardware irritation, facilitating earlier recovery of knee joint ROM, reducing the incidence of joint stiffness, and eliminating the need for additional removal surgery., Clinical Trial Number: Not applicable., Competing Interests: Declarations. Ethics approval and consent to participate: The study adhered to the principles of the Declaration of Helsinki and was approved by the Institutional Review Board (IRB) of Beijing Children’s Hospital ([2023]-E-179-R), which waived the need for consent to participate. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Background: Serum albumin (Alb) is an essential indicator of human physiological function, which can reflect the functionality of multiple organs, including the liver and kidneys. Presently, numerous studies have indicated that levels of blood albumin serve as important biomarkers for a range of respiratory illnesses. These findings can better guide clinical practice and disease prevention. However, there have been few investigations into the correlation between serum albumin and asthma. Therefore, this study aims to explore the relationship between serum albumin and the onset of asthma., Methods: Data from the 2003 to 2018 National Health and Nutrition Examination Survey (NHANES) were used in this observational study. Alb was measured using the bichromatic digital endpoint method. Univariate and multivariate logistic regression analyses of the potential correlation between Alb and asthma were performed. The non-linear relationship was characterized by restricted cubic spline (RCS) curve. We also conducted subgroup and interaction analyses., Result: In this study, we included 29,336 individuals with a mean age of 38.13 ± 17.98 years. Both univariate and multivariate logistic regression analyses show a significant association between serum albumin levels and asthma and higher Alb levels were associated with a lower risk of asthma (OR = 0.64, 95%CI: 0.43-0.96, p  = 0.032). RCS curve validated that serum albumin and asthma showed a biphasic correlation. The results of the subgroup analysis showed that a significant interaction between serum albumin and alcohol consumption, Alb was associated with reduced asthma risk only in the subgroup of non-alcohol drinkers (OR = 0.8, 95% CI: 0.7-0.93, p  < 0.001)., Conclusions: In the general population in the United States, asthma is associated with Alb, with asthma patients exhibiting lower albumin concentrations. This provides new insights into the management of asthma patients, suggesting that greater attention should be paid to their nutritional status, and further exploration of the causal relationship between the two may be warranted.

The performance of silver nanowire (AgNW) network flexible transparent electrodes is limited by large contact resistance, making it necessary to perform nanowelding to improve conductivity of the network. However, not all nanowire junctions can be welded. Our work indicates that the welding kinetics between nanowires depend on the crossing angle, with higher surface diffusion velocity prone to welding and fracture at nanowire junctions of crossing angles close to 90 degrees. The impact of nanowire crossing angles on the welding process makes it difficult to achieve simultaneous welding of random AgNWs networks. To address this issue, we adopted an improved Meyer rod coating method to prepared a cross-aligned nanowire network based on a layer-by-layer assembly strategy. Compared to randomly distributed AgNWs networks (11.17 Ω sq -1 , 85.2%), the cross-aligned AgNWs network achieved simultaneous welding of nanowire junctions during thermal annealing, further enhancing the optoelectronic performance (10.8 Ω sq -1 , 90.3%) of the AgNWs network, resulting in a superior figure of merit value of 421., (© 2025 IOP Publishing Ltd. All rights, including for text and data mining, AI training, and similar technologies, are reserved.)

The exploration of novel functionalized supramolecular coordination complexes (SCCs) can enable new applications in domains that include purification and sensing. In this study, employing a coordination-driven self-assembly strategy, we designed and prepared a series of benzochalcogenodiazole-based metallohelicates as high-efficiency charge-transfer surface-enhanced Raman scattering (SERS) substrates, expanding the range of applications for these metallohelicates. Through structural modifications, including the substitution of single heteroatoms on ligands, replacement of coordinating metals, and alteration of ligand framework linkages, the Raman performance of these metallohelicates as substrates were systematically optimized. Notably, the SERS enhancement factors (EFs) of the metallohelicate-based SERS substrates were significantly enhanced to levels as high as 1.03×10 7 , which rivals the EFs of noble metals devoid of "hot spots". Additionally, the underlying Raman enhancement mechanisms of these metallohelicates have been investigated through a combination of control experiments and theoretical calculations. This study not only demonstrates the utility of metallohelicates as SERS substrates but also offers insights and materials for the development of high-efficiency new charge-transfer SERS substrates., (© 2024 Wiley-VCH GmbH.)

Resistance to chemotherapy is a significant concern in the treatment of nasopharyngeal carcinoma (NPC), and occurs due to various mechanisms. This study is aimed to evaluate the effects of RING finger protein 138 (RNF138) in the development of cisplatin resistance to NPC. After gene overexpression and silencing, the expression levels of RNF138 were evaluated. The impacts of RNF138 on the proliferation and apoptosis rate of NPC cells were then assessed. γ-H2AX-mediated DNA damage was determined via immunofluorescence assay. Moreover, a tumor xenograft mouse model was developed to investigate the role of RNF138 on NPC progression in vivo. Additionally, transcriptome analysis was performed in 5-8 F cells transfection with OE-RNF1138 or OE-NC.Cisplatin significantly inhibited the proliferation, and promoted apoptosis and DNA damage in NPC cells; however, overexpression of RNF138 reversed the aforementioned regulatory role of cisplatin on NPC cells. Knockdown of RNF138 resulted in contrasting phenotypic outcomes. Additionally, in nude mice, RNF138 overexpression attenuated the suppressive effects of cisplatin on the growth of xenograft tumor, while RNF138 silencing further enhanced the inhibiting role of cisplatin. We further indicated that in 5-8 F cells following RNF138 overexpression, some pathways such as PI3K-Akt signaling pathway, human papillomavirus infection and ErbB signaling pathway that have been reported to be associated with NPC progression and cisplatin resistance were significantly enriched. These findings indicate that the modulation of RNF138 could potentially address the issue of chemotherapy failure by overcoming cisplatin resistance in NPC cells, making it a promising candidate for targeted drug therapy., Competing Interests: Declarations. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests. Conflict of interest: The authors declare no conflicts of interest. Ethics approval statement: This study was approved by the Ethical Committee of Taizhou Central Hospital (Taizhou University Hospital) (approval number: 2019-54). Permission to reproduce material from other sources: Not applicable., (© 2025. The Author(s).)

Deoxynivalenol (DON), a prevalent mycotoxin produced by Fusarium species, contaminates global agricultural products and poses significant health risks, particularly to the gastrointestinal (GI) system. DON exposure disrupts ribosomal function, inducing stress responses linked to various inflammatory diseases, including inflammatory bowel disease (IBD). In this study, we elucidate a novel regulatory mechanism involving ribosomal proteins (RPs) RPL13A and RPS3, which mediate proinflammatory chemokine production in DON-exposed gut epithelial cells. Through a combination of transcriptomic analysis and experimental models, we demonstrate that while RPL13A negatively regulates inflammation by enhancing the anti-inflammatory transcription factor ATF3, RPS3 acts as a proinflammatory driver, promoting chemokine production via activation of MAPK pathways, transcriptional upregulation of EGR-1, and stabilization of mRNA through cytosolic translocation of HuR. Our findings reveal a dynamic interplay between RPL13A and RPS3, wherein RPL13A counteracts the proinflammatory effects of RPS3, offering a finely tuned regulatory axis in the inflammatory response to environmental toxins. These insights provide potential molecular targets for therapeutic intervention in toxin-induced inflammatory diseases of the gut, highlighting the non-canonical roles of ribosomal proteins in modulating immune responses to environmental stressors., 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 © 2025 The Authors. Published by Elsevier Inc. All rights reserved.)

Lead halide perovskites are renowned for their exceptional optoelectronic properties but face concerns over lead toxicity and stability, which drives the exploration of lead-free perovskites, with Cs 2 AgBiBr 6 standing out as a benchmark alternative. Understanding the structural dynamics and thermal transport properties of Cs 2 AgBiBr 6 is crucial but remains an outstanding challenge due to the complex atomic fluctuations. Here, through diffuse scattering experiments and simulations, we uncover the underlying dynamic local structure in Cs 2 AgBiBr 6 , showing a unique two-dimensional spatial correlation. The inelastic X-ray scattering experiments and simulations further confirm the strong anharmonicity and short phonon lifetimes in Cs 2 AgBiBr 6 . An ultralow thermal conductivity of ∼0.36 W m -1 K -1 was measured by the frequency-domain thermoreflectance technique, with abnormal weak temperature dependence (∼ T -0.7 ). These results offer new insights into the lattice dynamics of lead-free double perovskites and are critical to understanding the electron-phonon and phonon-phonon couplings for their applications such as optoelectronics.

As a fundamental mechanism for gene expression regulation, post-transcriptional RNA methylation plays versatile roles in various biological processes and disease mechanisms. Recent advances in single-cell technology have enabled simultaneous profiling of transcriptome-wide RNA methylation in thousands of cells, holding the promise to provide deeper insights into the dynamics, functions, and regulation of RNA methylation. However, it remains a major challenge to determine how to best analyze single-cell epitranscriptomics data. In this study, we developed SigRM, a computational framework for effectively mining single-cell epitranscriptomics datasets with a large cell number, such as those produced by the scDART-seq technique from the SMART-seq2 platform. SigRM not only outperforms state-of-the-art models in RNA methylation site detection on both simulated and real datasets but also provides rigorous quantification metrics of RNA methylation levels. This facilitates various downstream analyses, including trajectory inference and regulatory network reconstruction concerning the dynamics of RNA methylation., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Adaptive control of solar light based on an optical switching strategy is essential to tune thermal gain, while real-time solar regulation and hence on-demand thermal management coupled with dynamic conditions still faces a formidable challenge. Herein, we develop a stacking structure which is mechanosensitive and can be finely tuned depending on the dynamic cavitation effect. Specifically, the stacking structure transfers from a solid monolith state to porous layered state progressively under mechanical stretching, and the resulting porous layered state gradually goes back to the solid monolith state once the load is released. Such structure switching results in gradual reversible optical transition from highly transparent to highly reflective, giving rise to high solar regulation capability coupled with continuous solar controllability. Based on this, the stacking structure functions allow multiple thermal management, not only for solar heating and radiative cooling, but also multi-stage thermoregulation and real-time thermal management on demand via a simple mechanical method. Moreover, the mechanosensitive stacking structure demonstrates impressive optical stability against external mechanical forces and extreme environments, with the combination of stability, durability, scalability, applicability, and self-cleaning ability.

The utilization of electrolyte additives has been regarded as an efficient strategy to construct dendrite-free aqueous zinc-ion batteries (AZIBs). However, the blurry screening criteria and time-consuming experimental tests inevitably restrict the application prospect of the electrolyte additive strategy. With the rise of artificial intelligence technology, machine learning (ML) provides an avenue to promote upgrading of energy storage devices. Herein, we proposed an intriguing ML-assisted method to accelerate the development efficiency of electrolyte additives on dendrite-free AZIBs. Concretely, we selected the Gutmann donor number (DN value) as a screen parameter, which can reflect the interaction between solvent molecules and ions, and proposed an integrated ML model that can predict the DN values of organic molecules via molecular fingerprints, thereby achieving the screening of electrolyte additives. Then, combined with experimental tests and theoretical calculations, the influence law of three additive molecules with different DN values on the thermodynamic stability of the Zn anode and its corresponding optimization mechanisms were revealed; the DN values of the additives are in positive correlation with the electrochemical performance of the Zn anode. Especially, an isopropyl alcohol (IPA) additive with a high DN value (36) integrated with various Zn-based cells presented a superior electrochemical performance, including a high calendar life (1500 h), a stable Coulombic efficiency (99% within 450 cycles), and a favorable cycling retention. This work pioneers ML techniques for predicting DN values for electrolyte additives, offering a compelling investigation method for the investigation of AZIBs.

Early weaning is frequently accompanied by a significant increase in diarrhea and mortality rates, which reduces rabbits' performance. Although antibiotics can reduce pathogenic bacteria, they also harm beneficial microorganisms and disrupt the normal intestinal microbiota balance. In order to find non-residue and non-toxic alternatives to antibiotics to ensure the safety of animal products, we conducted a study on the effect of compound microecological preparations supplementation on lactating female rabbits and their offspring. A total of 60 female rabbits were randomly assigned to four groups: CON, supplemented with probiotics at 3, 6, and 9 g/female rabbit/day from day 24 of gestation until weaning. We observed that probiotics supplementation significantly enhanced production performance ( P < 0.05), immune and antioxidant function ( P < 0.05), as well as intestinal flora composition in lactating rabbits and their offspring. Notably, compared with the control group, the experimental group exhibited a 19.23%, 44.22%, and 24.57% increase in milk yield ( P = 0.002). Regarding rabbit growth performance, the average body weight of young rabbits in the experimental group showed a significant increase of 3.59%, 10.22%, and 6.74% at day 35 ( P = 0.022), whereas the average daily gain (ADG) of rabbits aged between 21 and 35 days was significantly elevated by 4.94%, 17.06%, and 6.28% in the experimental group ( P < 0.001). In conclusion, probiotics supplementation can significantly enhance lactation performance, promote growth and disease resistance in rabbits, as well as improve intestinal health when administered at a dosage of 6 g/day. Moreover, the limited sample size in this study may hinder the detection of subtle effects, and augmenting the sample size will bolster the reliability of the study findings., Importance: The intestinal environment of rabbits is fragile and susceptible to environmental influences, leading to inflammatory intestinal diseases. Adding antibiotics to rabbit feed can achieve the effect of preventing and treating inflammation, which can also lead to the imbalance of the gut microbiota and residual antibiotics in agricultural products. Composite probiotics are live microbial feed additives composed of various ratios of probiotics and have become the most promising alternative to antibiotics due to their residue-free and non-toxic properties. The aim of this study was to investigate the impact of compound probiotics on lactating female rabbits and their offspring. Our findings highlight the potential of compound microecological preparations as an effective strategy for enhancing lactation performance, immune function, and antioxidant capacity in rabbits. The supplementation of probiotics through rabbit milk offers a promising approach to optimize the growth and health outcomes of newborn rabbits., Competing Interests: The authors declare no conflict of interest.

Background: The benefits of intravenous thrombolysis in patients with acute minor stroke remain controversial. For the aim of providing a better therapeutic strategy, high-quality trials are required to validate the efficacy of thrombolytic medicine other than intravenous recombinant tissue plasminogen and tenecteplase. In the trial, we evaluate the efficacy and safety of urokinase (UK) in acute minor stroke., Methods: This multicenter, open-label, blinded-endpoint, randomized controlled clinical trial enrolled patients with minor stroke within 6 h of symptom onset, with a NIHSS score ≤ 5. The trial was conducted at 25 hospitals in China between October 2020 and February 2023. Eligible patients were randomized to the UK group (1,000,000 U) or the best medicine treatment group. The responsible investigator recommended and implemented the best medicine treatment based on guidelines. The primary endpoint was an excellent functional outcome, defined as a modified Rankin scale (mRS) score of 0-1 at 90 days. The primary safety outcome was symptomatic intracranial hemorrhage (sICH) within 36 h., Results: A total of 999 patients were enrolled in the trial, the median age was 64 years, 371 (36.9%) were women; the median (IQR) NIHSS score was 3 (2-4). At 90 days, the primary endpoint was observed in 427 patients (84.9%) in the UK group and 425 patients (85.7%) in the control group (adjusted risk ratio [RR] 1.00, 95% CI 0.96-1.05, p = 0.87). A total of 3 patients in the UK-treated (0.6%) group experienced sICH compared to 1 patient (0.2%) in the control group (RR 1.83, 95% CI 0.16-20.27, p = 0.62)., Conclusions: For patients with acute minor stroke treated within 6 h of symptom onset, UK intravenous thrombolysis treatment was not found to be beneficial in terms of excellent functional outcome at 90 days, whereas it was safe., Trial Registration: ClinicalTrials.gov Identifier: NCT04420351., Competing Interests: Declarations. Ethics approval and consent to participate: The trial was approved by the Ethics Committees of the First Affiliated Hospital of Zhengzhou University (SS-2019-034) and of each participating site. Patients or their representatives provided informed consent before enrollment. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Adenosine 5'-triphosphate (ATP) plays a pivotal role as an essential intermediate in energy metabolism, influencing nearly all biological metabolic processes. Cancer cells predominantly rely on glycolysis for ATP production, differing significantly from normal cells. Real-time in situ monitoring and rapid response to intracellular ATP levels offers more valuable insights into cancer cell physiology. Herein, we report a novel ratiometric luminescent probe, Ru-Rho, comprised of a ruthenium(II)-based complex and rhodamine 6G (Rho 6G) with excellent water solubility and photostability. Notably, Ru-Rho selectively responds to ATP at acidic conditions, matching the need of monitoring ATP under the acidic intracellular environment of cancer cells. Moreover, the fast ratiometric detection and imaging of ATP under single wavelength excitation improve the detection accuracy. Ru-Rho has been effectively utilized not only for ratio imaging ATP in cells and zebrafish, but also for assessing the efficacy of glycolysis-inhibiting anticancer drugs in intracellular levels, which accelerates the screening process for anticancer drugs and supports the development of new therapeutic agents. The design strategy based on transition metal ruthenium(II) complexes opens a new pathway for constructing ATP luminescent probes, allowing for better adaptation to complex detection requirements., 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 © 2025 Elsevier B.V. All rights reserved.)

Background: The evolution and development of flowers are biologically essential and of broad interest. Maize and sorghum have similar morphologies and phylogeny while harboring different inflorescence architecture. The difference in flower architecture between these two species is likely due to spatiotemporal gene expression regulation, and they are a good model for researching the evolution of flower development., Results: In this study, we generated single nucleus and spatial RNA-seq data for maize ear, tassel, and sorghum inflorescence. By combining single nucleus and spatial transcriptome, we can track the spatial expression of single nucleus cluster marker genes and map single nucleus clusters to spatial positions. This ability provides great power to annotate the single nucleus clusters. Combining the cell cluster resolved transcriptome comparison with genome alignment, our analysis suggested that maize ear and tassel inflorescence diversity is associated with the maize-specific whole genome duplication. Taking sorghum as the outgroup, it is likely that the loss of gene expression profiling contributes to the inflorescence diversity between tassel and ear, resulting in the unisexual flower architecture of maize. The sequence of highly expressed genes in the tassel is more conserved than the highly expressed genes in the ear., Conclusion: This study provides a high-resolution atlas of gene activity during inflorescence development and helps to unravel the potential evolution associated with the differentiation of the ear and tassel in maize., Competing Interests: Declarations. Ethics approval and consent to participate: Not applicable. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Aortic dissection (AD) is a life-threatening aortopathy with no specific pharmacological therapy. Ubiquitination, a highly orchestrated enzymatic cascade involving sequential E1-E2-E3 interactions, is suggested to contribute to the disease pathogenesis. However, the specific role of E1 enzymes in AD progression remains unknown. In this study, we analyzed the aortic transcriptional profiles of a human ascending dissection dataset (GSE52093) and identified ubiquitin-like modifier-activating enzyme 1 (UBA1) as a significantly up-regulated E1 enzyme in human AD. This finding was further corroborated by immunohistochemistry and RT-qPCR in a mouse model of AD induced by β-aminopropionitrile (BAPN). Treatment of TAK-243, a specific UBA1 inhibitor, prevented BAPN-induced AD formation in mice and attenuated aortic medial degeneration, as evidenced by decreased elastin fragmentation (evaluated by EVG scoring), reduced vascular smooth muscle cell loss (visualized by α-SMA immunohistochemistry), and less extracellular matrix degradation (indicated by diminished MMP2 and MMP9 expression in immunohistochemistry and RT-qPCR). Furthermore, TAK-243 treatment attenuated lesional macrophage accumulation and activation, as demonstrated by CD68 immunohistochemistry and RT-qPCR analysis of aortic pro-inflammatory cytokine expression. In vitro, UBA1 activation was observed in macrophages (RAW264.7 cells) treated with angiotensin II (AngII), and TAK-243 significantly reduced AngII-induced macrophage activation, at least partially through the inhibition of IκBα and NF-κB p65 phosphorylation. In conclusion, we demonstrate that UBA1 may facilitate AD progression by promoting macrophage activation via the NF-κB signaling pathway. These findings reveal a pathogenic role for the E1 enzyme UBA1 in AD and show a pharmacological potential of UBA1-targeted therapy against this disease., 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 selective cleavage of C-N bonds in N-containing compounds holds significant research value in organic synthesis, particularly for the synthesis of promising polynitrogen species. For instance, the discovery of the cyclo-pentazolate (cyclo-N 5 - ) anion in 2017 as a result of cleavage of the C-N bond has sparked interest within the field of high energy density materials. However, previous methods using ferrous glycinate and m-chloroperoxybenzoic acid generated the cyclo-N 5 - anion in a low yield of 19.5 % after 24 hours, and the mechanism remained unclear. In this study, we developed an efficient catalytic system comprising Mn (II) tetraphenylporphyrin and cumyl hydroperoxide. This system enables the cyclo-N 5 - anion to be produced from 3,5-dimethyl-4-hydroxyphenylpentazole in 35.4 % yield in 4 hours. Characterization of Mn(IV)-oxo porphyrins, ⋅ CH 3 , and ⋅ C 8 H 8 ON 5 radicals provides evidence for the mechanism whereby the cyclo-N 5 - anion forms. Our study underscores the competitive potential of radical-initiated selective C-N bonds cleavage in N-arylazoles and opens avenues for further exploration in this field., (© 2024 Wiley-VCH GmbH.)

Mimicking the superstructures and properties of spherical biological encapsulants such as viral capsids 1 and ferritin 2 offers viable pathways to understand their chiral assemblies and functional roles in living systems. However, stereospecific assembly of artificial polyhedra with mechanical properties and guest-binding attributes akin to biological encapsulants remains a formidable challenge. Here we report the stereospecific assembly of dynamic supramolecular snub cubes from 12 helical macrocycles, which are held together by 144 weak C-H hydrogen bonds 3 . The enantiomerically pure snub cubes, which have external diameters of 5.1 nm, contain 2,712 atoms and chiral cavities with volumes of 6,215 Å 3 . The stereospecific assembly of left- and right-handed snub cubes was achieved by means of a hierarchical chirality transfer protocol 4 , which was streamlined by diastereoselective crystallization. In addition to their reversible photochromic behaviour, the snub cubes exhibit photocontrollable elasticity and hardness in their crystalline states. The snub cubes can accommodate numerous small guest molecules simultaneously and encapsulate two different guest molecules separately inside the uniquely distinct compartments in their frameworks. This research expands the scope of artificial supramolecular assemblies to imitate the chiral superstructures, dynamic features and binding properties of spherical biomacromolecules and also establishes a protocol for construction of crystalline materials with photocontrollable mechanical properties., Competing Interests: Competing interests: The authors declare no competing interests., (© 2025. The Author(s), under exclusive licence to Springer Nature Limited.)

Organic cathode materials are widely considered as highly promising for aqueous zinc-ion batteries (AZIBs) due to their tunable properties, low cost, and ease of processing and synthesis. Benzothiadiazoles have demonstrated significant potential as organic electrode materials in AZIBs, owing to their strong electron-accepting capabilities and the presence of multiple reversible redox sites in anthraquinone. In this study, we designed a polymer, poly(2-methyl-6-(7-methyl-5,6-dinitrobenzo[ c ][1,2,5]thiadiazol-4-yl)anthracene-9,10-dione) (PBDQ), with multielectron transfer capability through a copolymerization approach. Additionally, we synthesized another polymer, poly2,6-bis(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)anthracene-9,10-dione(PBDQ-N), by introducing two electron-withdrawing nitro groups on the aromatic ring of benzothiadiazole. The introduction of nitro groups, with their unique electronic properties, enhances electron delocalization and increases the number of electrochemically active sites, thereby promoting faster zinc-ion insertion/extraction reactions. Experimental results show that both PBDQ and PBDQ-N exhibit excellent electrochemical properties due to the abundance of active sites and extended π-conjugation. Among them, PBDQ-N demonstrates outstanding performance, including an ultrahigh specific capacity of 446.2 mAh g -1 at 0.1 A g -1 and excellent cycle life exceeding 20,000 cycles at 10 A g -1 . Moreover, the lower lowest-unoccupied molecular orbital (LUMO) energy level and improved conductivity of PBDQ-N provide a fast electron transfer rate, resulting in a higher Zn 2+ diffusion coefficient (3.47 × 10 -11 -2.6 × 10 -8 cm 2 s -1 ) and exceptional rate performance (234.6 mAh g -1 at 10 A g -1 ). Theoretical calculations and ex situ characterizations confirm that C═O, C═N, and N═O groups all participate as active sites in Zn 2+ storage. This work highlights how molecular design and the introduction of functional groups, such as nitro groups, can effectively regulate the electrochemical properties of organic polymers in AZIBs. It also demonstrates the impact of these strategies on the electrochemical performances of these materials when they are used as cathodes in aqueous zinc-ion batteries.

Insulin-like growth factor 2 (IGF2) is a mitogenic peptide hormone expressed by various tissues. Although it is three times more abundant in serum than IGF1, its physiological and pathological roles are yet to be fully understood. Previous transcriptome sequencing studies have shown that IGF2 expression is increased in hypertrophic scar (HS); however, its role in HS formation and the underlying mechanism remains elusive. The present study found that IGF2 expression was significantly higher in HS than in normal skin (NS), particularly in epidermal cells. Moreover, mechanical stretch increased IGF2 expression and secretion in keratinocytes, affecting the biological activities of fibroblasts, including proliferation, migration, and collagen synthesis, and transdifferentiated into myofibroblasts after co-culturing keratinocytes with fibroblasts. Mechanistically, keratinocyte-secreted IGF2 activated a nuclear transcription factor phosphorylated c-Jun (p-c-Jun) through insulin-like growth factor 1 receptor (IGF1R) on fibroblast cytomembrane, thereby triggering the profibrotic effect of IGF2. Blocking IGF1R or p-c-Jun inhibited the IGF2-induced profibrotic effect of fibroblasts. Moreover, increased p-c-Jun expression restored the reduction in fibrosis induced by IGF1R knockdown. The IGF2 recombinant protein was also applied to a mouse wound-healing scar model. It was found that IGF2 significantly promoted the formation of HS, whereas IGF2 small molecule inhibitor chromeceptin inhibited HS formation. In conclusion, this study demonstrates that mechanical stretch-induced IGF2 overexpression in epidermal keratinocytes promotes fibroblast activation through the IGF1R/p-c-Jun axis. Therefore, IGF2 may act as a therapeutic target for HS., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Boron dipyrromethene (BODIPY)-based zirconium metal-organic frameworks (Zr-MOFs) possess strong light-harvesting capabilities and great potential for artificial photosynthesis without the use of sacrificial reagents. However, their direct preparation has not yet been achieved due to challenges in synthesizing suitable ligands. Herein, we reported the first successful direct synthesis of BODIPY-based Zr-MOFs, utilizing CO 2 as a feedstock. By controlling synthetic conditions, we successfully obtained two distinct Zr-MOFs. The first, CO 2 -Zr 6 -DEPB, exhibits a face-centered cubic (fcu) topology based on a Zr 6 (μ 3 -O) 4 (μ 3 -OH) 4 node, while the second, CO 2 -Zr 12 -DEPB, features a hexagonal closed packed (hcp) topology, structured around a Zr 12 (μ 3 -O) 8 (μ 3 -OH) 8 (μ 2 -OH) 6 node. Both MOFs demonstrated excellent crystallinity, as verified through powder X-ray diffraction and high-resolution transmission electron microscopy analyses. These MOF catalysts displayed suitable photocatalytic redox potentials for the reduction of CO 2 to CO using H 2 O as the electron donor in the absence of co-catalyst or toxic sacrificial reagent. Under light irradiation, CO 2 -Zr 12 -DEPB and CO 2 -Zr 6 -DEPB offered high CO yields of 16.72 and 13.91 μmol g -1  h -1 , respectively, with nearly 100 % selectivity. CO 2 uptake and photoelectrochemical experiments revealed key insights into the mechanisms driving the different catalytic activities of the two MOFs. These BODIPY and CO 2 -based, light-responsive Zr-MOFs represent a promising platform for the development of efficient photocatalysts., (© 2025 Wiley-VCH GmbH.)

Oncolytic viruses are emerging as promising cancer therapeutic agents, with several poxviruses, including vaccinia virus (VACV) and myxoma virus, showing significant potential in preclinical and clinical trials. Modified vaccinia virus Ankara (MVA), a laboratory-derived VACV strain approved by the FDA for mpox and smallpox vaccination, has been shown to be incapable of replicating in human cells unless zinc finger antiviral protein (ZAP) is repressed. Notably, ZAP deficiency is prevalent in various cancer types. We hypothesized that MVA could selectively target and replicate in ZAP-deficient cancer cells. Our study examined MVA's replication across multiple cancer cell lines with varying ZAP expression levels, revealing that MVA replicates more efficiently in cells with lower ZAP expression. Additionally, we assessed MVA's oncolytic potential using a xenograft mouse model, where cancer cells were transplanted into immunodeficient mice. The data demonstrated that MVA significantly reduced tumors with lower ZAP expression without causing morbidity in nude mice. These findings suggest that MVA holds promise for further development as a targeted therapy for ZAP-deficient cancers., (© 2024 Wiley Periodicals LLC.)

Objective: To explore the microstructural damage of white matter in acute diquat (DQ) poisoning patients using diffusion kurtosis imaging (DKI) and Tract-based Spatial Statistics (TBSS)., Methods: This study included 19 DQ poisoning patients and 19 age-matched controls. MRI was performed using a 3.0 T Philips Achieva scanner with sequences including 3D T1WI, T2WI, DWI, 3D T2WI-FLAIR, and DKI (3 b-values, 15 directions). DICOM to NIFTI image form conversion was done using MRIcron's Dcm2niigui, followed by motion and eddy current correction with FSL to create a brain mask. Scalar indicators (MK, AK, RK, FAK) were calculated with DKE software. TBSS was used for spatial normalization, skeletonization, and projection of DKI indices for group analysis with TFCE for multiple comparison correction (P < 0.025)., Results: After the screening and enrollment process, 19 DQ-poisoned patients and 19 healthy volunteers were analyzed. No significant age or sex differences were found between groups. For Mean Kurtosis (MK), the right corticospinal tract showed a significant difference with a mean difference of 0.21 (95 % CI: 0.15-0.27) and P = 0.000503. Axial Kurtosis (AK) in the left superior longitudinal fasciculus had a mean difference of 0.18 (95 % CI: 0.12-0.24) and P = 0.0024. Fractional Anisotropy of Kurtosis (FAK) in the right corticospinal tract showed a mean difference of 0.19 (95 % CI: 0.13-0.25) and P = 0.0000318. Axial Kurtosis (AK) positively correlated with blood drug levels (r = 0.52, P < 0.05). Seven patients developed subcortical leukodystrophy, mainly in the frontal parietal lobe, with possible insular lobe involvement., Conclusions: DQ poisoning primarily damages the right corticospinal tract, right cingulate gyrus, and left superior longitudinal fasciculus, potentially causing movement and visual impairments. The injury involves demyelination and axonal degeneration, with asymmetrical damage between hemispheres. The left superior longitudinal fasciculus injury is dose-dependent, and unlike prior studies, dopaminergic nuclei were unaffected. The frontal parietal lobe is predominantly affected, with some insular lobe involvement in DQ poisoning patients., 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.)

Tea leaf spot, caused by the fungus Didymella segeticola, occurs in the high-mountain tea plantations of Southwest China. Due to a limited understanding of the disease's epidemiology and the lack of comprehensive control measures, it has a significant negative impact on tea yield and quality. In this study, we revealed that D. segeticola infection begins when conidia germinate to form a germ tube on the leaf surface. The fungus then grows in the intercellular spaces of the leaf epidermal cells, invading tea tissue and causing necrotic lesions. This infection leads to significant alterations in the cell walls of spongy and palisade mesophyll cells, severely damaging chloroplasts. We employed transcriptomic and metabolomic analyses based on an in vitro infection model using matcha powder to uncover two key genes of D. segeticola: DsHAD (encoding holoacid dehydrogenase) and DsADH (encoding alcohol dehydrogenase). These genes are associated with conidiation, virulence, and sensitivity to oxidative stress. DsHAD regulates the virulence of D. segeticola by modulating glutamate homeostasis. Our results elucidate the infection strategy of D. segeticola on tea leaves and provide valuable data for future research on control measures for tea leaf spot., 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. Published by Elsevier B.V.)

Background: Thrombomodulin, a thrombin receptor with anticoagulant, anti-inflammatory, and cytoprotective properties, has been suggested to play a pivotal role in ischemic stroke. However, the association of plasma thrombomodulin with post-stroke cognitive impairment (PSCI) remains unclear. We aimed to prospectively investigate the associations of plasma thrombomodulin with PSCI among ischemic stroke patients in a multicenter cohort study., Methods: We measured plasma thrombomodulin levels at baseline among 615 ischemic stroke patients from a preplanned ancillary study of the CATIS (China Antihypertensive Trial in Acute Ischemic Stroke). We used Montreal Cognitive Assessment (MoCA) to evaluate cognitive function at 3-month follow-up after ischemic stroke, and PSCI was defined as MoCA score <23., Results: Plasma thrombomodulin was inversely associated with PSCI, and the adjusted odds ratio of PSCI for the highest versus lowest quartile of thrombomodulin was 0.50 (95 % CI: 0.28-0.92, P trend =0.026). Each standard deviation increment of log-transformed thrombomodulin was associated with a 23 % (odds ratio: 0.77, 95 % CI: 0.62-0.97, P=0.029) decreased risk of PSCI. In addition, plasma thrombomodulin could significantly improve the risk reclassification of PSCI beyond established risk factors (net reclassification index: 25.04 %, 95 % CI: 7.20 %-42.87 %, P=0.007; integrated discrimination improvement: 1.13 %, 95 % CI: 0.18 %-2.09 %, P=0.020)., Conclusions: High plasma thrombomodulin levels were associated with a decreased risk of PSCI among ischemic stroke patients. Our findings suggest that plasma thrombomodulin might be a predictive biomarker and potential therapeutic target for PSCI., Competing Interests: Declaration of competing interest There are no conflicts of interest to declare., (Copyright © 2024. Published by Elsevier Inc.)

Background: Lack of a dedicated thrombectomy device for cerebral venous thrombosis hinders the recanalization ability of endovascular treatment (EVT). Novel NiTi-braided stent retriever (Venous-TD) is a dedicated venous sinus thrombectomy device. This study aims to demonstrate the safety and efficacy of Venous-TD., Methods: In this pilot, prospective, randomized, single-blind, parallel-group control, single-center clinical study, patients with cerebral venous thrombosis from Beijing Xuanwu Hospital were included. Randomization was performed to EVT with either the Venous-TD or Angioguard with Sterling balloon (control group). The primary efficacy outcome was the proportion of immediate complete recanalization during EVT. Secondary outcomes included the proportion of functional independence and moderate to severe residential headache at 180 days after EVT. Safety outcomes included peri-procedural complications, all-cause mortality, and symptomatic intracranial hemorrhage after EVT., Results: A total of 61 patients were enrolled and randomized. Thirty-one patients were randomized to the Venous-TD group, and 30 were randomized to the control group. The median (interquartile range) age was 28 (21-45) in the Venous-TD group and 34 (24-43) in the control group. The proportion of patients with a National Institutes of Health Stroke Scale score >8 on admission was 8 (25.8%) in the Venous-TD group and 11 (36.7%) in the control group. During EVT, Venous-TD significantly improved the proportion of complete recanalization compared with Angioguard (23 [76.7%] versus 6 [20.0%]; relative risk, 3.833 [95% CI, 1.825-8.054]). The proportions of long-term functional independence at 180 days in the Venous-TD group and the control group were not significantly different. The proportion of patients with severe residual headache at 180 days in the Venous-TD group was significantly lower than that in the control group (3 [9.7%] versus 10 [35.7%]; relative risk, 0.271 [95% CI, 0.083-0.886]). Safety outcomes showed no statistically significant difference between the 2 groups., Conclusions: This trial indicated that Venous-TD did not increase complications in EVT of cerebral venous thrombosis and can significantly increase the proportion of complete recanalization. A multicenter phase III randomized control trial assessing efficacy and safety of Venous-TD is warranted., Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT05291585., Competing Interests: The Venous-TD device was developed by Xuanwu Hospital Capital Medical University and produced by Beijing Honghai Microtech, Co, Ltd. The authors report no conflicts.

Non-coding RNAs play crucial roles in plant responses to viral stresses. However, their molecular mechanisms in tea leaf spot responses remain unclear. In this study, using Camellia sinensis, we identified lncRNA81246 as a long non-coding RNA that localizes to both the nucleus and cytoplasm. It functions as a competitive endogenous RNA, thereby disrupting CsNAC1 (encoding NAC domain-containing protein 1) degradation mediated by miR164d. Silencing lncRNA81246 increased the resistance of tea plants to presistanceathogens, whereas transient lncRNA81246-overexpression plants showed decreased resistance to pathogens. Co-expression assays in Nicotiana benthamiana revealed that lncRNA81246 affects the miR164d-CsNAC1 regulatory module. Transient miR164d-overexpression and silencing assays demonstrated its positive regulation of tea plant resistance. Specifically, silencing its target, CsNAC1, enhanced disease resistance, whereas transient overexpression reduced plant resistance. Yeast one-hybrid, dual-luciferase, and RT-qPCR assay results suggested that CsNAC1 alters the expression of CsEXLB1, whereas AsODN and tobacco transient overexpression assays showed that CsEXLB1 negatively regulated tea plant resistance. Thus, our research demonstrated that lncRNA81246 acts as a mediator to interfere with the miR164d-CsNAC1 regulatory module involved in the disease resistance of tea plants., (© 2024 The Author(s). The Plant Journal published by Society for Experimental Biology and John Wiley & Sons Ltd.)

Hypertension is a major preventable risk factor for cardiovascular disease, affecting over 1.5 billion adults worldwide. Antihypertensive peptides (AHTPs) have gained attention as a natural therapeutic option with minimal side effects. This study proposes a Deep Forest-based machine learning framework for AHTP prediction, leveraging a multi-granularity cascade structure to enhance classification accuracy. We integrated data from BIOPEP-UWM and three previously used datasets, totaling 2000 peptide sequences, and introduced novel feature extraction methods to build a comprehensive dataset for model training. This study represents the first application of Deep Forest for AHTP identification, demonstrating substantial classification performance advantages over traditional methods (e.g., SVM, CNN, and XGBoost) as well as recent mainstream prediction models (Ensemble-AHTPpred, CNN-SVM Ensemble, and mAHTPred). Requiring no complex manual feature engineering, the model adapts flexibly to various data needs, offering a novel perspective for efficient AHTP prediction and promising utility in hypertension management. On the benchmark dataset, the model achieved high accuracy, sensitivity, and AUC, providing a robust tool for identifying safe and effective AHTPs. However, future efforts should incorporate larger and more diverse independent validation datasets to further improve the model and enhance its generalizability. Additionally, the model's predictive accuracy relies on known AHTP targets and sequence features, potentially limiting its ability to detect AHTPs with uncharacterized or atypical properties., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2024. Published by Elsevier B.V.)

As a promising approach for breast cancer treatment, photothermal therapy (PTT) features high spatial selectivity, noninvasiveness, and minimal drug resistance. IR780 (a near-infrared fluorescent dye) serves as an effective photosensitizer in PTT cancer therapy. However, the clinical application of IR780 in PTT has been hindered by its poor water solubility and unstable photostability. In this study, a genetically engineered dual-functional fusion protein tLyP-1-MGF6 is successfully constructed and expressed, which presents a novel use of hydrophobin MGF6 for its amphiphilicity combined with the tumor-penetrating peptide tLyP-1 to create an innovative carrier for IR780. These results show this fusion protein serving as a biodegradable and biocompatible carrier, significantly improves the water solubility of IR780 when formulated into nanoparticles. These studies demonstrate that the IR780@tLyP-1-MGF6 nanoparticles significantly enhance tumor targeting and photothermal therapeutic efficacy in comparison with control in vitro and in vivo. These advancements highlight the potential of the unique combination hydrophobin-based IR780 delivery system as a multifunctional nanoplatform for integrated imaging and targeted photothermal treatment of breast cancer., (© 2024 Wiley‐VCH GmbH.)

Carbonaceous materials have been considered the most promising anode in sodium-ion batteries (SIBs) due to their low cost, good electrical conductivity, and structural stability. The main challenge of carbonaceous anodes prior to their commercialization is low initial coulomb efficiencies, derived from a lack of an efficient technique to reveal a fundamental comprehension of sodium storage mechanisms. Here, the direct observation of quasi-Na metallic clusters in carbonaceous anodes during cycling through in situ XRD is reported. By means of such a technique, a strong self-adsorption behavior forming quasi-Na metallic clusters is detected within a rationally designed highly defective ultrathin carbon nanosheets (HDCS) anode. Such a self-adsorption and crystalline system transformation mechanism in HDCS brings capacity retention about 100% after 1000 cycles at 1 A g -1 . This work provides a new principle for designing high-performance carbon anodes for SIBs., (© 2024 Wiley‐VCH GmbH.)

Parkinson's disease (PD) pathogenesis is characterized by α-synuclein (α-syn) pathology, which is influenced by various factors such as neuroinflammation and senescence. Increasing evidence has suggested a pivotal role for Interleukin-17A(IL-17A) and Interleukin-17 Receptor A (IL-17RA) in PD, yet the trigger and impact of IL-17A/IL-17RA activation in PD remains elusive. This study observed an age-related increase in IL-17A and IL-17RA in the human central nervous system, accompanied by increased α-syn and senescence biomarkers. Interestingly, both levels of IL-17A and IL-17RA in PD patients were significantly elevated compared to age-matched controls, wherein the IL-17A was mainly present in neurons. This abnormal neuronal IL-17A activation in the PD brain was recapitulated in α-syn mouse models. Correspondingly, administration of recombinant IL-17A exacerbated pathological α-syn in both neuron and mouse models. Furthermore, IL-17A/IL-17RA pathway interventions via blocking antibody or shRNA-mediated knockdown can mitigate the effects of pathological α-syn. This study reveals an interplay between dysregulation of the IL-17A/IL-17RA pathway and α-syn, suggesting that regulating the IL-17A/IL-17RA pathway could modify PD progression by disrupting the detrimental cycle., 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. Published by Elsevier Inc.)

Meat quality is a key factor influencing consumer purchasing decisions. Muscle composition consists of various types of myofibers (type I and type IIa, IIb, IIx myofibers), and the relative composition of fiber types has a significant impact on the overall biochemical properties and flavor of fresh meat. However, the relationship between biochemical changes in myofibers and their impact on meat quality remains underexplored. In this study, we compared the differences in meat quality by examining different muscles in rabbits, each containing different muscle fiber types. We focused on the adductor (ADD) and semitendinosus (ST) as our research subjects and investigated skeletal muscle metabolism at the individual myofibers level using Spatial metabolomics. Additionally, we utilized LC-MS and RNA-Seq to explore the molecular mechanisms underlying the metabolic differences between red and white muscle fibers. Our findings demonstrated that variations in myofiber composition significantly influenced meat color, pH, water content, and drip loss. Spatial metabolomics analysis identified 22 unique red and white muscle fingerprint metabolites, while LC-MS analysis revealed 123 differential metabolites, and these differential metabolites were mainly enriched in the pathways of ABC transporters, Biosynthesis of amino acids, glutathione metabolism, and arginine biosynthesis. To further elucidate the molecular mechanism of differential metabolism in ADD and ST, we identified 2248 differentially expressed genes (DEGs) by RNA-Seq and then combined DEGs with DMs for joint analysis. We found that red muscle exhibited higher levels of metabolites such as L-glutamic acid, glutathione, ascorbate, ornithine, oxidized glutathione, gamma-L-glutamyl-L-cysteine, cysteinylglycine, fumaric acid, gamma-aminobutyric acid. Additionally, related metabolic genes such as MGST1, ODC1, MGST3 and PRDX6 were highly expressed in ST muscle. These metabolites and genes were enriched in the glutathione and nicotinamide pathways, and had significant effects on meat color and drip loss. Moreover, red muscle contained more flavor compounds and nutrients, including adenosine monophosphate (AMP), ornithine, citrulline, taurine, acetyl phosphate, L-glutamic acid metabolites, as well as taurine and hypotaurine metabolites. Our results demonstrate that fresh meat with a higher proportion of red muscle fibers exhibited superior meat quality, enhanced flavor, and higher nutrient content. Furthermore, red muscle contains more antioxidant metabolites that can effectively prevent meat oxidation during the production process., 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 use of dressings in clinical settings is common for the purpose of wound wrapping and creating an optimal microenvironment to enhance the healing process. Proper coverage of wounds with dressings serves as the fundamental basis for effective wound healing. Unfortunately, non-standard coverage by hands can cause pain and secondary damage to patients, while slow manual application during treatment of extensive burns may increase the risk of wound infection. Herein, drawing inspiration from the microstructure and hygroscopic deformation observed in pine cones, we propose a polyvinyl alcohol/polysulfone (PVA/PSF) smart dressing. This bioinspired smart dressing exhibits rapid bending deformation under high moisture condition, allowing easy adjustment of bending amplitude, speed, and direction. Moreover, the smart dressing is capable of rapid bending and autonomous wrapping around "artificial wounds" on a doll's body, as well as fitting irregularly shaped "hand wounds" and extensive "arm wounds" on human subjects. By integrating two layers into one dressing design, we endow it with dual functionality: The hygroscopic PVA layer facilitates transversal liquid transport to effectively reduce exudate accumulation in the wound bed while maintaining proper moisture levels; meanwhile, the highly hydrophobic PSF layer repels various aqueous solutions to protect against external contaminants. In vivo results confirm that this multifunctional smart dressing promotes collagen synthesis and accelerates angiogenesis for accelerated wound healing. We believe that this innovative multifunctional approach to wound management will provide valuable insights into wound healing therapy., 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.)

Surveillance recommendations for gastric cancer (GC) in current guidelines focused on advanced precancerous lesions and were based on precise diagnosis of severity/extent of baseline lesions. We aimed to develop a less endoscopy-related equipment-dependent risk-stratification tool, and assessed whether mild-precursor-lesion patients can be safely exempt from surveillance. In the multicenter community-based cohort, 75,051 participants receiving baseline endoscopy were enrolled during 2015-2017 and followed-up until 2021. Cumulative incidence rates (CIRs) of GC for precancerous-conditions were calculated by Kaplan-Meier method and compared by Log-rank tests. Mixed-effects Cox regression models were used to detect potential factors for progression towards GC. A risk score was calculated as counts of selected factors. An independent cohort, including 26,586 participants was used for external validation. During a median follow-up of 6.25 years, CIRs of GC were 0.302%, 0.436%, and 4.756% for normal group, non-neoplastic (atrophic gastritis/intestinal metaplasia) and neoplastic lesions (low-grade/high-grade dysplasia), respectively (P trend <0.001). Four predictors, including male, ⩾60 years, smoking, and limited vegetable consumption, were selected for risk-stratification. High-risk patients (⩾3 risk factors) with non-neoplastic lesions showed higher GC risks (adjusted HR=7.73, 95%CI: 4.29-13.92), and their four-year CIR reached the one-year CIR of neoplastic lesions. Further categorizing non-neoplastic lesions by histological grade, both patients with moderate-to-severe lesions (aHR=3.07, 95%CI: 1.67-5.64) and high-risk patients with mild lesions (aHR=7.29, 95%CI: 3.58-14.86) showed higher risks. Consistent trends were observed in validation cohort. High-risk mild-precursor-lesion patients should receive surveillance within 3-5 years after baseline screening. Our study provides evidence on supplementing current guideline recommendations., Competing Interests: Compliance and ethics. All authors have no potential conflicts to disclose. The protocol of this study has been approved by the ethics committee of National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College (2015SQ00223). The protocol of ESLCSP (external validation) has also been approved by the ethics committee of National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College (NCC-1788). All the participants have provided written informed consent., (© 2024. Science China Press.)

Objectives: This study aimed to evaluate the potential of deep learning (DL)-assisted automated three-dimensional quantitative tumor burden at MRI to predict postoperative early recurrence (ER) of hepatocellular carcinoma (HCC)., Materials and Methods: This was a single-center retrospective study enrolling patients who underwent resection for BCLC A and B HCC and preoperative contrast-enhanced MRI. Quantitative total tumor volume (cm 3 ) and total tumor burden (TTB, %) were obtained using a DL automated segmentation tool. Radiologists' visual assessment was used to ensure the quality control of automated segmentation. The prognostic value of clinicopathological variables and tumor burden-related parameters for ER was determined by Cox regression analyses., Results: A total of 592 patients were included, with 525 and 67 patients assigned to BCLC A and B, respectively (2-year ER rate: 30.0% vs. 45.3%; hazard ratio (HR) = 1.8; p = 0.007). TTB was the most important predictor of ER (HR = 2.2; p < 0.001). Using 6.84% as the threshold of TTB, two ER risk strata were obtained in overall (p < 0.001), BCLC A (p < 0.001), and BCLC B (p = 0.027) patients, respectively. The BCLC B low-TTB patients had a similar risk for ER to BCLC A patients and thus were reassigned to a BCLC A n stage; whilst the BCLC B high-TTB patients remained in a BCLC B n stage. The 2-year ER rate was 30.5% for BCLC A n patients vs. 58.1% for BCLC B n patients (HR = 2.8; p < 0.001)., Conclusions: TTB determined by DL-based automated segmentation at MRI was a predictive biomarker for postoperative ER and facilitated refined subcategorization of patients within BCLC stages A and B., Clinical Relevance Statement: Total tumor burden derived by deep learning-based automated segmentation at MRI may serve as an imaging biomarker for predicting early recurrence, thereby improving subclassification of Barcelona Clinic Liver Cancer A and B hepatocellular carcinoma patients after hepatectomy., Key Points: Total tumor burden (TTB) is important for Barcelona Clinic Liver Cancer (BCLC) staging, but is heterogenous. TTB derived by deep learning-based automated segmentation was predictive of postoperative early recurrence. Incorporating TTB into the BCLC algorithm resulted in successful subcategorization of BCLC A and B patients., Competing Interests: Compliance with ethical standards. Guarantor: The scientific guarantor of this publication is Bin Song, M.D. Conflict of interest: H.W.: no relevant relationships. T.Z.: no relevant relationships. X.Z., C.Z., and D.J.: employees of Shukun Technology Co., Ltd. Y.W.: no relevant relationships. J.M.L.: no relevant relationships. M.R.B.: research grants to the institution from Siemens Healthineers, Madrigal Pharmaceuticals, NGM Biopharmaceuticals, Carmot Therapeutics, and Corcept Therapeutics; associate editor for contrast media section of Radiology; associate editor for continuing medical education of Journal of Magnetic Resonance Imaging. E.L.: no relevant relationships. R.L.: no relevant relationships. B.W.: no relevant relationships. H.G.: no relevant relationships. Y.C.: no relevant relationships. T.Y.: no relevant relationships. X.G.: no relevant relationships. H.J.: stock owner of Kanghong Technology Co., Ltd. B.S.: no relevant relationships. Statistics and biometry: One co-author (Yuanan Wu, Big Data Research Center, University of Electronic Science and Technology of China, Chengdu, Sichuan 610000, China) has significant statistical expertise. Informed consent: The requirement for informed consent was waived (retrospective design) by the Biomedical Ethics Review Committee of West China Hospital, Sichuan University. Ethical approval: The study protocol was approved by the Biomedical Ethics Review Committee of West China Hospital, Sichuan University (Approval Numbers: 2022-651). Study subjects or cohorts overlap: Some study subjects (37.5%, 222/592) have been previously reported in another study. While the prior work proposed a preoperative prognostic score for overall survival, the current work focused on exploring three-dimensional quantitative tumor burden biomarkers for predicting postsurgical early recurrence of hepatocellular carcinoma. Methodology: Retrospective Diagnostic or prognostic study Single-center study, (© 2024. The Author(s).)

Background: Peripheral artery disease (PAD) is a significant vascular condition that can lead to severe complications, including limb ischemia and cardiovascular events. This meta-analysis aims to evaluate the association between prediabetes, an intermediate state between normoglycemia and diabetes, and the risk of developing PAD., Methods: A comprehensive search of PubMed, EMBASE, and Web of Science databases was conducted to identify relevant cohort studies up to April 12, 2024. Data extraction was performed independently by 2 reviewers, and any discrepancies were resolved by consensus. Pooled risk ratios (RRs) and 95% confidence intervals (CIs) were calculated using a random effects model to account for heterogeneity among studies., Results: A total of 8 cohort studies comprising 90,133 participants were included in the meta-analysis. The pooled analysis revealed that individuals with prediabetes had a significantly higher risk of PAD compared to those with normoglycemia (RR = 1.27; 95% CI: 1.13-1.42; P < 0.001; I 2  = 55%). Subgroup analyses indicated that the association was stronger in prediabetes defined by mildly elevated hemoglobin A1c (RR: 1.47) compared to those defined by impaired fasting glucose (RR: 1.21) or impaired glucose tolerance (RR: 1.17, p for subgroup difference <0.001). In addition, a stronger association was observed for studies reporting clinically diagnosed PAD compared to studies that included asymptomatic PAD (RR: 1.32 vs. 0.92; p for subgroup difference = 0.02)., Conclusions: This meta-analysis demonstrates a significant association between prediabetes and an increased risk of PAD in a generally community-derived population., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Polyphenols have received considerable attention for their promotive effects on colonic health. However, polyphenols are mostly sensitive to harsh gastrointestinal environments, thus, must be protected. It is necessary to design and develop a colon-targeted delivery system to improve the stability, colon-targeting and bioavailability of polyphenols. This paper mainly introduces research on colon-targeted controlled release of polyphenols. The physiological features affecting the dissolution, release and absorption of polyphenol-loaded delivery systems in the colon are first discussed. Simultaneously, the types of colon-targeted carriers with different release mechanisms are described, and colon-targeting assessment models that have been studied so far and their advantages and limitations are summarized. Based on the current research on polyphenols colon-targeting, outlook and reflections are proposed, with the goal of inspiring strategic development of new colon-targeted therapeutics to ensure that the polyphenols reach the colon with complete bioactivity.