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The electrocatalytic nitrite reduction (NO 2 RR) converts nitrogen-containing pollutants to high-value ammonia (NH 3 ) under ambient conditions. However, its multiple intermediates and multielectron coupled proton transfer process lead to low activity and NH 3 selectivity for the existing electrocatalysts. Herein, we synthesize a solid-solution copper-zinc cyanamide (Cu 0.8 Zn 0.2 NCN) with localized structure distortion and tailored surface electrostatic potential, allowing for the asymmetric binding of NO 2 - . It exhibits outstanding NO 2 RR performance with a Faradaic efficiency of ∼100% and an NH 3 yield of 22 mg h -1 cm -2 , among the best for such a process. Theoretical calculations and in situ spectroscopic measurements demonstrate that Cu-Zn sites coordinated with linear polarized [NCN] 2- could transform symmetric [Cu-O-N-O-Cu] in CuNCN-NO 2 - to a [Cu-N-O-Zn] asymmetric configuration in Cu 0.8 Zn 0.2 NCN-NO 2 - , thus enhancing adsorption and bond cleavage. A paired electro-refinery with the Cu 0.8 Zn 0.2 NCN cathode reaches 2000 mA cm -2 at 2.36 V and remains fully operational at industrial-level 400 mA cm -2 for >140 h with a NH 3 production rate of ∼30 mg NH3 h -1 cm -2 . Our work opens a new avenue of tailoring surface electrostatic potentials using a solid-solution strategy for advanced electrocatalysis.

Background: Understanding the allocation of nitrogen (N) and phosphorous (P) among various plant organs is crucial for gaining insights into plant nutrient uptake, utilization strategies, and overall growth and life history strategies. However, little is known about the nitrogen and phosphorus allocation strategies among the three major plant organs (e.g., leaves, stems, and roots), particularly in phylogenetically closely related species. To investigate N and P allocation strategies among different plant organs, we collected 912 individuals of 62 Artemisia species, encompassing three subgenera, from 81 sites across a broad environmental expanse in China., Results: Average N and P concentration and N: P ratios in major plant organs of Artemisia species have significant variations among the subgenera and ecosystems. Across all 62 species, the numerical values of the scaling exponents of N(α N ), P(α P ), and N: P(α N: P ) between leaves and stems, and leaves and root were consistently more than 1, while the corresponding scaling exponents for stems versus roots were either close to or less than 1; however, the numerical values of the scaling exponents among the three plant organs differed at subgenera levels but were relatively consistent across different ecosystems. Climate and soil had little effect on the numerical values of the scaling exponents among plant organs of Artemisia species at different local sites., Conclusion: Our results found that the allocation of N and P among plant organs in Artemisia species differs at the subgenera level, suggesting that it is necessary to consider different subgenus levels when exploring plant nutrient concentration and allocation. Conversely, a conservative nutrient allocation strategy prevails at the ecosystem level. Thus, a key insight from these results is that nutrient allocation strategies of closely related species are phylogenetically conserved and are comparatively insensitive to local environmental conditions., Competing Interests: Declarations. Ethics approval and consent to participate: The research was performed in accordance with Chinese law and international guidelines. The field experiments and plants sampling were approved by the ethical approval committee of Chinese Academy of Sciences. The plant samples in this study are not endangered species. All plant species in our study were identified by Prof. Xuejun Yang from Institute of Botany, the Chinese Academy of Sciences. Voucher specimens were deposited in the herbarium of Institute of Botany, the Chinese Academy of Sciences. All methods of this study complied with relevant institutional, national, and international guidelines and legislation. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Background: The dysfunction of mitochondria has been associated with the development of sepsis, but the specific mitochondrial-related genes and their roles in sepsis have not been fully elucidated. We employed Mendelian randomization and colocalization analysis to investigate the association between mitochondrial-related genes and sepsis by integrating multi-omics data., Methods: Summary-level data on mitochondrial gene methylation, expression, and protein abundance levels were obtained from corresponding studies on methylation, expression, and protein quantitative trait loci, respectively. Genetic associations with sepsis were obtained from the genome-wide association studies catalog database. We used the MitoCarta3.0 database, which contains an updated list of 1,136 human mitochondrial genes, to identify mitochondrial genes. To assess the associations between mitochondrial gene-related molecular features and sepsis, we conducted summary data-based Mendelian randomization analysis. In addition, we performed colocalization analysis to determine whether the identified signal pairs shared a causal genetic variant., Results: After integrating the multi-omics data between methylation quantitative trait loci- expression quantitative trait loci and expression quantitative trait loci-protein quantitative trait loci, we identified FIS1 as having tier 1 evidence for its association with sepsis. Methylation of cg01299997 in FIS1 was found to be associated with lower expression of FIS1, an increased risk of sepsis, and a positive role in cg01299997 methylation. Furthermore, NUDT2, IMMP2L, LYRM4, MRPL10, MRPL17, MTIF3, and TFAM genes were associated with sepsis risk with tier 2 evidence. Both gene expression and protein abundance levels of NUDT2 were observed to be associated with an increased risk of sepsis. In addition, the ATP5MC1 and VWA8 genes were associated with sepsis risk with tier 3 evidence. Among these tertiary genes, ATP5MC1 gene expression level showed a negative correlation (posterior probability of H4 = 0.9242), whereas the gene expression level of VWA8 exhibited a positive correlation (posterior probability of H4 = 0.7270)., Conclusion: We found that the mitochondrial FIS1, NUDT2, IMMP2L, LYRM4, MRPL10, MRPL17, MTIF3, TFAM, ATP5MC1, and VWA8 genes were putatively associated with sepsis risk with evidence from multi-omics levels. This study identified mitochondrial genes in relation to sepsis, which may enhance the understanding of the pathogenic mechanisms of sepsis development., Competing Interests: Conflict of Interest/Disclosure The authors declare that they have no competing interests., (Copyright © 2025 The Author(s). Published by Elsevier Inc. All rights reserved.)

Cancer stem cells (CSCs) possess the ability to self-renew and exhibit high differentiation potential, and they have been proven to be responsible for the maintenance, growth, and metastasis of tumors. As such, accurate identification and targeted therapy for CSCs are of great importance in clinical treatment. Here, a dual-targeted and light-responsive nanoprobe is presented, utilizing the reconstructed mesoporous SiO 2 of a binary fatty acid eutectic mixture and a gold porous shell. The gold shell in the nanoprobe sustains a large absorption cross-section, providing a robust photothermal treatment effect against CSCs upon NIR irradiation. The photothermal effect simultaneously melts the eutectic mixture, which acted as the gating material, triggering the release of nuclear-targeted photosensitizers for photodynamic therapy (PDT). Additionally, to improve the hypoxic environment during PDT, hemoglobin (Hb) is conjugated to the nanoprobe using disulfide as a cross-linker, which can consume cellular glutathione while releasing Hb to deliver oxygen for PDT. Under the synergistic effect of photothermal therapy (PTT) and PDT, cytoplasmic organelles and intranuclear genetic materials are hierarchically damaged, initiating a cascade of reactions, including evident endoplasmic reticulum stress and inflammation. These responses, in turn, promote stem cell death and inhibit tumorigenicity. Furthermore, machine learning models, including random forest (FR), CatBoost, XGBoost, and LightGBM, were employed to optimize the reaction conditions for maximizing the synergistic effect, with CatBoost achieving the best performance. Additionally, antibody-conjugated nanoprobes effectively targeted colon cancer stem cells, demonstrating enhanced phototoxicity and the potential to suppress tumorsphere formation. Therefore, this dual-targeting nanoprobe demonstrates outstanding therapeutic integration performance and shows promise as a platform for synergistic PTT/PDT therapy of CSCs.

Tryptophan participates in important life activities and is involved in various metabolic processes. The indole and aromatic binuclear ring structure in tryptophan can engage in diverse interactions, including π-π, π-alkyl, hydrogen bonding, cation-π, and CH-π interactions with other side chains and protein targets. These interactions offer extensive opportunities for drug development. In this letter, we have designed and synthesized a series of linear oligopeptides adorned with tryptophan residues and identified their potential targets through artificial intelligence-assisted technology and experimental verification. In vitro bioactivity assays revealed that the oligopeptides containing Gly-Pro-Trp residues exhibited promising antitumor activity by inducing autophagy and apoptosis. The PharmMapper pharmacophore mapping approach, molecular docking, and molecular dynamics simulations together identified poly(ADP-ribose) polymerase 1 (PARP1), an enzyme associated with chromatin regulation, as the potential target for the designed compounds. Experimental biolayer interferometry (BLI) and enzyme-linked immunosorbent assay (ELISA) have verified that the oligopeptides could bind with PARP1 and influence PARP1 expression levels. A quantitative structure-activity relationship has been established between the chemical structures of the prepared compounds and their IC 50 values. In summary, the research presents a feasible approach for exploring oligopeptide-based antitumor agents.

We report here a Cu 2+ -doped layered double hydroxide (LDH) nanoplatform to load both monocarboxylate transporter inhibitor diclofenac (DC) and lactate oxidase (LOX) for dual modulation of tumor lactate and redox metabolisms to activate immunotherapy through enhanced Cu-mediated chemodynamic therapy (CDT) of tumors. The formed LDH-DC-LOX nanoparticles with a diameter of 55 nm are stable, can be effectively taken up by cancer cells to regulate lactate through both LOX-mediated catalytic conversion and DC-enabled inhibition of extracellular efflux of lactate, and can exert redox metabolism through CDT via Cu 2+ -mediated glutathione (GSH) depletion and Fenton-like reaction with hydrogen peroxide (H 2 O 2 ) that can be further accumulated via LOX-mediated catalysis. The major advantage of the developed LDH-DC-LOX nanoparticles lies in the therapeutic synergy and cascade that can be achieved through the loaded DC and LOX for enhanced tumor lactate metabolism regulation, for enhanced Cu-mediated CDT and redox metabolism regulation, and for activation of immunotherapy that can further enhances the Cu 2+ -mediated CDT effect. The developed LDH nanoplatform demonstrated here for effective murine breast tumor treatment provides a new paradigm for dual regulation of lactate and redox metabolisms that may enable synergistic and cascaded combination therapy of different cancer types. STATEMENT OF SIGNIFICANCE: Targeting the tumor microenvironment (TME) to alter tumor metabolic pathways represents a promising strategy for next-generation cancer therapy. Herein, a copper-doped layered double hydroxide (LDH) nanoplatform is developed to co-deliver both diclofenac (DC) and lactate oxidase (LOX) to tumor cells for efficient dual regulation of tumor lactate and redox metabolisms, resulting in synergistic and cascaded chemodynamic therapy/immunotherapy of breast tumors. The developed LDH-DC-LOX nanoparticles can release Cu 2+ and DC under an acidic TME, and can act in synergy to reduce TME lactate and generate H 2 O 2 , thus modulating redox metabolism and activating anticancer immunotherapy. The secreted cytokine IFN-γ after activation of antitumor immune responses can further mediate enhanced chemodynamic therapy effect through downregulation of cystine/glutamate transporter SLC7A11 to suppress GSH synthesis., 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 Acta Materialia Inc. Published by Elsevier Inc. All rights reserved.)

Hepatobiliary magnetic resonance imaging (MRI) is a crucial diagnostic tool for early detection and staging of liver tumors. However, the currently available hepatobiliary-specific contrast agents (CAs), acyclic Gd chelates, suffer from limited kinetic stability and may pose serious toxicity risks to patients with specific functional impairments. In light of these concerns, Mn-based MRI CAs have gained increasing attention as potential alternatives to Gd-based agents, despite challenges in their stability and relaxivity. Herein, we present a novel hepatobiliary-specific CA in the form of Mn(II)-based metal-organic framework (MOF) nanoparticles conjugated with ethoxybenzyl-poly(ethylene glycol) (EOB-PEG) ligands. These nanoparticles exhibit significantly higher relaxivity ( r 1 = 66.4 mM -1 s -1 in 4.5% HSA) compared to a commercial hepatobiliary-specific CA, Gd-EOB-DTPA ( r 1 = 11.2 mM -1 s -1 in 4.5% HSA), along with excellent biocompatibility. This enables them to achieve equivalent imaging contrast with a substantially lower metal concentration (0.025 mmol Mn 2+ per kg BW vs. 0.1 mmol Gd 3+ per kg BW for the commercial Gd-EOB-DTPA). Furthermore, our MOF-based nanoparticles demonstrate precise diagnostic capabilities in vivo , as evidenced by their performance in orthotopic HCC mouse models. This progress holds great promise for the development of advanced hepatobiliary-specific CAs, which could significantly enhance early liver cancer diagnosis by providing clearer and safer imaging options.

Background: Tandem repeats (TRs) are abundant in the human genome and associated with repeat expansion disorders. Our study aimed to develop a tandem repeat panel utilizing targeted long-read sequencing to evaluate known TRs associated with these disorders and assess its clinical utility., Methods: We developed a targeted long-read sequencing panel for 70 TR loci, termed dynamic mutation third-generation sequencing (dmTGS), using the PacBio Sequel II platform. We tested 108 samples with suspected repeat expansion disorders and compared the results with conventional molecular methods., Results: For 108 samples, dmTGS achieved an average of 8000 high-fidelity reads per sample, with a mean read length of 4.7 kb and read quality of 99.9%. dmTGS outperformed repeat-primed-PCR and fluorescence amplicon length analysis-PCR in distinguishing expanded from normal alleles and accurately quantifying repeat counts. The method demonstrated high concordance with confirmatory methods (rlinear = 0.991, P < 0.01), and detected mosaicism with sensitivities of 1% for FMR1 CGG premutation and 5% for full mutations. dmTGS successfully identified interruptive motifs in genes that conventional methods had missed. For variable number TRs in the PLIN4 gene, dmTGS identified precise repeat counts and sequence motifs. Screening 57 patients with suspected genetic muscular diseases, dmTGS confirmed repeat expansions in genes such as GIPC1, NOTCH2NLC, NUTM2B-AS1/LOC642361, and DMPK. Additionally, dmTGS detected CCG interruptions in CTG repeats in 8 myotonic dystrophy type 1 patients with detailed characterization., Conclusions: dmTGS accurately detects repeat sizes and interruption motifs associated with repeat expansion disorders and demonstrates superior performance compared to conventional molecular methods., (© Association for Diagnostics & Laboratory Medicine 2024. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Facioscapulohumeral muscular dystrophy type 1 (FSHD1) patients exhibit marked variability in both age at onset (AAO) and disease severity. Early onset FSHD1 patients are at an increased risk of severe weakness, and early onset has been tentatively linked to the length of D4Z4 repeat units (RUs) and methylation levels. The present study explored potential relationships among genetic characteristics, AAO and disease severity in FSHD1. This retrospective and observational cohort study was conducted at the Fujian Neuromedical Centre (FNMC) in China. Genetically confirmed participants with FSHD1 recruited from 2001 to 2023 underwent distal D4Z4 methylation assessment. Disease severity was assessed by FSHD clinical score, age-corrected clinical severity score (ACSS) and onset age of lower extremity involvement. Mediation analyses were used to explore relationships among genetic characteristics, AAO and disease severity. Finally, machine learning was employed to explore AAO prediction in FSHD1. A total of 874 participants (including 804 symptomatic patients and 70 asymptomatic carriers) were included. Multivariate Cox regression analyses indicated that male gender, low DUZ4 RUs, low CpG6 methylation levels, non-mosaic mutation and de novo mutation were independently associated with early onset in FSHD1. Early onset patients (AAO < 10 years) had both a significantly higher proportion and an earlier median onset age of lower extremity involvement compared to the typical adolescent onset (10 ≤ AAO < 20 years), typical adult onset (20 ≤ AAO < 30 years) and late onset (AAO ≥ 30 years) subgroups. AAO was negatively correlated with both clinical score and ACSS. We found that AAO exerted mediation effects, accounting for 12.2% of the total effect of D4Z4 RUs and CpG6 methylation levels on ACSS and 38.6% of the total effect of D4Z4 RUs and CpG6 methylation levels on onset age of lower extremity involvement. A random forest model that incorporated variables including gender, age at examination, inheritance pattern, mosaic mutation, D4Z4 RUs and D4Z4 methylation levels (at CpG3, CpG6 and CpG10 loci) performed well for AAO prediction. The predicted AAO (pAAO) was negatively correlated with ACSS (Spearman's ρ = -0.692). Our study revealed independent contributions from D4Z4 RUs, D4Z4 methylation levels, mosaic mutation and inheritance pattern on AAO variation in FSHD1. AAO mediates effects of D4Z4 RUs and methylation levels on disease severity. The pAAO values from our random forest model informatively reflect disease severity, offering insights that can support efficacious patient management., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Selenium (Se) is an essential trace element for human health, and dietary Se intake is an effective supplement. Rich in nutrients and functional components with potential for Se enrichment, Tartary buckwheat ( Fagopyrum tataricum (L.) Gaertn.) is a Se-biofortified cereal. To determine the optimal Se treatment concentration and fully understand its effects on Tartary buckwheat, sodium selenite (Na 2 SeO 3 ) in different concentrations was sprayed onto leaves of Tartary buckwheat at the initial flowering stage. Agronomic and yield-related traits and Se enrichment were analyzed between CK and treatments. The results showed that Na 2 SeO 3 concentrations of 3.0 and 6.0 mg/L significantly increased the contents of Se and starch in the grains, the 1000-grain weight, the number of grains per plant, and the yield. The 6.0 mg/L treatment had the best effect. Transcriptome and weighted gene co-expression network analyses showed that selenite promoted chlorophyll synthesis and photoelectron transport by upregulating chlorophyll synthase (CHLG) and protein CURVATURE THYLAKOID 1B (CURT1B) levels, improving photosynthesis, increasing sucrose synthesis and transport in leaves and starch synthesis and accumulation in grains, and promoting grain-filling and yield. These changes were regulated by genes related to photosynthesis, sucrose, and starch metabolism-related genes, including CAB3C , HPR3 , SUS5 , BAM9 , SS3 , SWEET1 , and SWEET12 . Selenite absorption in Tartary buckwheat was regulated by aquaporin genes NIP1-1 and PIP1-5 . Selenite transport was regulated by the inorganic phosphate transporter gene PHT1-1 , and organic Se transport was controlled by the proton-dependent oligopeptide transporters NPF3.1 and NPF4.6. Methionine gamma-lyase (MGL) was involved in selenocompound metabolism. This study identified the best spraying scheme for enhancing Se content in the grains. It also revealed the regulatory genes responding to selenite absorption, transport, and metabolism and the regulatory pathways promoting yield in Tartary buckwheat. These results provide technical guidance and theoretical support for producing high-yielding and Se-enriched Tartary buckwheat.

Background: Circulating proteins in blood are involved in various physiological processes, but their contributions to blood pressure regulation remain partially understood. In traditional observational studies, identifying circulating proteins causally associated with blood pressure is challenging because of potentially unmeasured confounding and possible reverse causality., Methods: Two-sample Mendelian randomization analyses were conducted to estimate the causal effects of 2270 circulating proteins (data sourced from 8 genome-wide association studies) on diastolic blood pressure, systolic blood pressure, and pulse pressure. Colocalization analyses were then used to investigate whether the circulating proteins and blood pressure traits shared causal genetic variants. To further verify the findings, we subsequently performed Steiger filtering analyses, annotation of protein-altering variants, assessment of overlap between protein quantitative trait loci and expression quantitative trait loci, protein-protein interaction and functional enrichment analyses, and drug target evaluation. To provide more potential biomarkers, we further evaluated the epidemiological associations of 2923 circulating proteins with blood pressure and hypertension by cross-sectional and longitudinal analyses using individual data in the UK Biobank., Results: Mendelian randomization and colocalization analyses identified 121 circulating proteins with putative causal effects on at least 1 blood pressure trait. Many of the identified proteins are enriched in the pathways relevant to blood pressure regulation, and a majority of these proteins are either known drug targets or druggable candidates., Conclusions: This study has uncovered numerous circulating proteins potentially causally associated with blood pressure, providing insights into the regulatory mechanisms of blood pressure and potential therapeutic targets to facilitate blood pressure management., Competing Interests: None.

Metal halide perovskites (MHPs) have achieved substantial progress in their applications; however, their ionic crystal character and low formation energy result in poor structural stability and limited morphological tunability. In particular, high relative humidity (RH) commonly causes severe MHP degradation, which poses a major obstacle to long-term device operation. Herein, high RH-induced growth of anisotropic MHP structures on glass surfaces is reported under 25 °C and atmospheric conditions on a basis of glass corrosion by moisture. Nanowires (NWs) with tunable length and composition are obtained under 85% RH air, and water molecule-induced facet engineering of perovskite is established for anisotropic growth. Importantly, single-mode photonic lasing in these MHP NWs with thickness at sub-100-nm scale (down to 75 nm ∼ 1/7 lasing wavelength) is achieved via both one-photon and multiphoton pumping. These nanowire lasers exhibited high quality factor (>3000), high degree of polarization (≈0.9), and excellent stability under laser irradiation. The work not only presents a distinctive technique for the growth of MHPs but also endows MHP NWs with new opportunities for nonlinear optics, strong light-matter interactions, and active photonic integrated devices., (© 2024 The Author(s). Advanced Science published by Wiley‐VCH GmbH.)

Inhibition of aldose reductase (AR) activity is promising for mitigating diabetic complications. Defatted evening primrose seeds (DO), a byproduct of evening primrose oil production, exhibits significant AR inhibitory effects. This study optimized extraction conditions of DO using response surface methodology to maximize the recovery of AR inhibitors (ARIs). A combination of high-speed countercurrent chromatography, affinity-based ultrafiltration, and high-performance liquid chromatography was used to screen ARIs from DO extract. Five compounds were identified as ARIs, with avicularin, a minor ARI, demonstrating the strongest inhibitory activity (IC 50  = 4.17 μg mL -1 ). The inhibitory kinetics and interaction mechanisms of avicularin against AR were investigated, revealing that avicularin acts as a non-competitive inhibitor of AR (K i  = 4.42 μM). Avicularin quenched the intrinsic fluorescence of AR through static quenching, forming non-covalent complexes primarily via hydrogen bonds and van der Waals forces, while also altering the conformational structure and microenvironment of AR, impairing AR activity., 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 Ltd. All rights reserved.)

The plasmid-borne resistance gene mcr drastically undermines the effectiveness of colistin, posing a substantial threat to public health. Although several key plasmid elements that balance mcr-1 persistence and bacterial growth are identified, the regulatory interactions between mcr-1 and host bacteria remain poorly understood. Using a genome-wide CRISPRi crRNA library, it is identified that DNA polymerase IV, dinB, is essential for controlling the fitness cost associated with mcr-1 in Escherichia coli. The absence of dinB operon enhances mcr-1-mediated colistin resistance but simultaneously compromises bacterial growth and competitiveness. Meanwhile, dinB deficiency mitigates inflammatory response in RAW267.4 cells and enhances bacterial colonization in murine tissues. Further investigation reveals that mcr-1 actively upregulates dinB expression, with the increased reactive oxygen species induced by mcr-1 being crucial for this activation.   These findings suggest that dinB modulates mcr expression and bacterial fitness via a negative feedback regulatory mechanism. Leveraging this regulatory relationship, a Toxin-Intein is engineered under the control of dinB promoter to selectively target and kill mcr-positive E. coli both in vitro and in vivo. Overall, the work uncovers a novel adaptive mechanism underlying mcr persistence and provides a precise antimicrobial strategy to combat antibiotic-resistant pathogens., (© 2025 The Author(s). Advanced Science published by Wiley‐VCH GmbH.)

In the field of Structural Health Monitoring (SHM), complete datasets are fundamental for modal identification analysis and risk prediction. However, data loss due to sensor failures, transmission interruptions, or hardware issues is a common problem. To address this challenge, this study develops a method combining Variational Mode Decomposition (VMD) and Sparrow Search Algorithm (SSA)-optimized Gate Recurrent Unit (GRU) for recovering structural response data. The methodology initially employs Variational Mode Decomposition (VMD) to preprocess and decompose the existing data from the target sensor into Intrinsic Mode Functions (IMFs) and residuals. Subsequently, the Gated Recurrent Unit (GRU) network utilizes data from other sensors to reconstruct the IMFs and residuals, ultimately producing the data reconstruction results. During this process, Singular Spectrum Analysis (SSA) is used to optimize the hyperparameters of the GRU network. To validate the effectiveness of this method, we utilized one month of monitoring data collected from a certain project and a publicly available dataset. On the public dataset, we tested performance at different data loss rates. Results show that, compared to a standalone GRU model and a VMD + GRU model, the VMD + SSA + GRU model's reconstruction data root mean squared error is reduced by 46.61% and 32.57% on average, respectively, while the coefficient of determination increases by 38.74% and 18.50%. The data reconstruction method proposed in this study can accurately capture trends in missing data, without the need for manual hyperparameter tuning, and the reconstruction results are highly consistent with the real data., Competing Interests: Declarations. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Background: Increased systemic bone mineral density has been reported in patients with ossification of the posterior longitudinal ligament (OPLL). This study investigated the differences in vertebral Hounsfield unit (HU) values between the bridged and nonbridged groups of patients with OPLL of the cervical spine at the ossification-related segments., Methods: A total of 436 ossification-related segments from 157 patients were involved in the study. X-ray and computed tomography scans were used to assess the segmental cervical range of motion (ROM), C2-7 Cobb angle, K-line, ossification thickness, maximum canal occupancy, HU values, and presence and type of OPLL., Results: In terms of imaging parameters, HU values were significantly higher in the OPLL group (P < 0.001), whereas the ROM was greater in the control group (P < 0.05). In the OPLL group, the K-line positive group had a better C2-7 Cobb angle and greater T1 slope. The ossification-related segments were divided into bridging and nonbridging groups, with smaller vertebral HU values, thicker ossification lesions, greater canal occupation, and reduced interbody mobility in the bridging group. However, we found no significant correlation among segmental ROM, ossified material thickness, maximum canal occupancy of the ossified material, and segmental HU values., Conclusions: We found that the mean HU value of the cervical spine in patients with OPLL was higher than that of the control group, and the ROM was smaller than that of the control group, with the smallest ROM in the continuous type. In the ossification-related segments, the bridging group exhibited lower vertebral HU values, reduced segmental mobility, and thicker ossification thickness., (Copyright © 2024. Published by Elsevier Inc.)

Background: Fasting-mimicking diet (FMD) boosts the antitumour immune response in patients with colorectal cancer (CRC). The gut microbiota is a key host immunity regulator, affecting physiological homeostasis and disease pathogenesis., Objective: We aimed to investigate how FMD protects against CRC via gut microbiota modulation., Design: We assessed probiotic species enrichment in FMD-treated CRC mice using faecal metagenomic sequencing. The candidate species were verified in antibiotic-treated conventional and germ-free mouse models. Immune landscape alterations were evaluated using single-cell RNA sequencing and multicolour flow cytometry. The microbiota-derived antitumour metabolites were identified using metabolomic profiling., Results: Faecal metagenomic profiling revealed Bifidobacterium pseudolongum enrichment in FMD-treated CRC mice. B. pseudolongum mediates the FMD antitumour effects by increasing the tissue-resident memory CD8 + T-cell (TRM) population in CRC mice. The level of L-arginine, a B. pseudolongum functional metabolite, increased in FMD-treated CRC mice; furthermore, L-arginine induced the TRM phenotype in vivo and in vitro. Mechanistically, L-arginine is transported by the solute carrier family 7-member 1 (SLC7A1) receptor in CD8 + T cells. Both FMD and B. pseudolongum improved anti-CTLA-4 efficacy in the orthotopic mouse CRC model. In FMD-treated patients with CRC, the CD8 + TRM cell number increased as B. pseudolongum and L-arginine accumulated. The abundance of CD8 + TRM cells and B. pseudolongum was associated with a better prognosis in patients with CRC., Conclusion: B. pseudolongum contributes to the FMD antitumour effects in CRC by producing L-arginine. This promotes CD8 + T-cell differentiation into memory cells. B. pseudolongum administration is a potential CRC therapeutic strategy., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2025. No commercial re-use. See rights and permissions. Published by BMJ Group.)

Introduction: The core objective of this study was to precisely locate metastatic lymph nodes, identify potential areas in nasopharyngeal carcinoma patients that may not require radiotherapy, and propose a hypothesis for reduced target volume radiotherapy on the basis of these findings. Ultimately, we reassessed the differences in dosimetry of organs at risk (OARs) between reduced target volume (reduced CTV2) radiotherapy and standard radiotherapy., Methods and Materials: A total of 209 patients participated in the study. We used image registration techniques to map patients' neck metastatic lymph nodes onto a template CT of healthy individuals. Using MIM software, we integrated all patients' lymph node images onto the template CT images and conducted an in-depth analysis of their distribution characteristics and metastatic patterns. Subsequently, we randomly selected the localization images of 30 patients and used paired t test methods to compare the differences in the dosimetry of target volumes and OARs between reduced target volume radiotherapy and standard radiotherapy., Results: A total of 2314 metastatic lymph nodes were identified and mapped. There were no metastatic lymph nodes observed at level VIIb or within the lateral border of the common carotid artery. The percentages of metastatic lymph nodes at levels Ia, Ib, IIa, IIb, III, IVa, IVb, Va, Vb, Vc, VIa, VIb, VIIa, VIIb and VIII accounted for 0%, 1.5%, 22.8%, 41.1%, 15.9%, 3.0%, 0%, 4.4%, 1.0%, 0.3%, 0%, 0%, 9.7%, 0% and 0.3%, respectively, of the 2314 metastatic lymph nodes. Further analysis of the dosimetric outcomes revealed a significantly lower mean dose to the oral cavity, laryngeal cavity, esophagus, trachea, pharyngeal constrictor muscles, parotid gland, submandibular gland and thyroid gland with the implementation of reduced-target radiotherapy than with standard radiotherapy., Conclusion: IMRT sparing level I, IVb, VI, and VIIb lymph nodes and the area within the lateral border of the common carotid artery for stage II-IVa NPC patients is feasible. This method can significantly reduce the dose to peripheral organs at risk., Competing Interests: Declarations. Ethics approval and consent to participate: The Clinical Research Ethics Committee of the First Affiliated Hospital of Kunming Medical University approved this study, and the participants provided written informed consent. This research was conducted in compliance with the Declaration of Helsinki. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

To simplify the composition and improve the efficacy of metal-phenolic network (MPN)-based nanomedicine, herein, we designed an MPN platform to deliver programmed death ligand-1 (PD-L1) antibody (anti-PD-L1) for combined tumor chemo/chemodynamic/immune therapy. Here, generation 5 poly(amidoamine) dendrimers conjugated with gossypol (Gos) through boronic ester bonds were used as a synthetic polyphenol to coordinate Mn 2+ , and then complexed with anti-PD-L1 to obtain the nanocomplexes (for short, DPGMA). The prepared DPGMA exhibited good water dispersibility with a hydrodynamic size of 166.3 nm and tumor-microenvironment-responsive drug release behavior. The integration of Gos and Mn 2+ within the DPGMA resulted in significant tumor inhibition and immunogenic cell death activation through Gos-mediated chemotherapy and Mn 2+ -catalyzed chemodynamic therapy, respectively, thereby leading to significant dendritic cell maturation due to the role of Mn 2+ played to mediate the activation of the stimulator of interferon genes (STING) pathway. Moreover, the complexed anti-PD-L1 promoted the recognition and uptake of nanocomplexes by PD-L1-overexpressed tumors through antibody targeting, thereby achieving combinational chemo/chemodynamic/immune therapy in a mouse melanoma model, where the immunotherapy modes combined three parts of activation via chemotherapy/CDT-mediated ICD, Mn 2+ -mediated STING activation, and antibody-mediated immune checkpoint blockade. With the Mn 2+ -endowed r 1 relaxivity (1.38 mM -1 s -1 ), the DPGMA nanocomplexes can also be used for tumor MR imaging. The designed dendrimer-mediated MPN platform may be developed as an advanced nanomedicine to tackle other cancer types.

With the evolution of consumer purchasing power and consumption concepts, external attributes such as fruit size, color, and peel smoothness have emerged as pivotal determinants influencing purchasing preferences; among these, the background color of the fruit peel exerts a considerable impact on fruit esthetics. The background color of fruit peel is predominantly influenced by the chlorophyll content. Consequently, examining the degradation patterns of chlorophyll in Prunus persica L. peel holds significant importance for cultivating varieties with a cleaner peel background color. In this study, Prunus persica L. CP14 and 20-29 were selected as experimental materials to evaluate the peel color variation and chlorophyll content during fruit development. Samples collected from three developmental stages of CP14 and 20-29 underwent transcriptome sequencing. Kyoto Encyclopedia of Genes and Genomes enrichment analysis identified chlorophyll-degradation-related genes within the purine metabolism pathway. Quantitative polymerase chain reaction analysis of chlorophyll degradation gene expression pinpointed PpPAO and PpSGR as likely key genes involved in chlorophyll degradation in Prunus persica L. Transient transformation assays in Nicotiana benthamiana leaves further substantiated that PpPAO and PpSGR markedly reduce chlorophyll levels. Yeast two-hybrid experiments also demonstrated an interaction between PpPAO and PpSGR .

Extubation failure rates are notably high in patients in neurointensive care. Ineffective cough is the variable independently associated with extubation failure, but its quantification remains challenging. Patients with primary central nervous system injury requiring invasive mechanical ventilation were included. After a successful spontaneous breathing trial (SBT), abdominal muscles and diaphragm ultrasound were performed under tidal breathing and coughing. 98 patients were initially recruited for the study, and 40 patients were ultimately included in the final analysis. Extubation failure occurred in 8 (20%) patients. Rectus abdominis (RA) and internal oblique (IO) muscles showed difference regarding cough thickening fraction (TF) between the extubation success and failure group (P < 0.05). The logistic regression that analysis suggested cough TFRA, cough TFIO and cough TIO were the factors associated with extubation outcome (P < 0.05). In the receiver operating characteristic analysis, cough TFIO exhibited the strongest predictive value (AUC = 0.957, 95% CI:0.8979-1). A threshold of cough TFIO ≥ 34.15% predicted extubation success with a sensitivity of 93.8% and specificity of 75%. Abdominal muscles ultrasound was a promising tool to predict extubation for patients requiring neurointensive care.Trial registration: The study was registered on Chinese Clinical Trial Registry: ChiCTR2400088210, Registered 13 August 2024 - Retrospectively registered, https://www.chictr.org.cn/bin/project/edit?pid=234150 ., Competing Interests: Declarations. Competing interests: The authors declare no competing interests. Ethics approval and consent to participate: This study got the approval of the local ethics committee of The First Affiliated Hospital of Fujian Medical University, Fuzhou, China (MRCTA, ECFAH of FMU [2024] 380). The contacts of the ethics committee are: 0086–0591 − 87,981,028, fykyll@163.com, and No.20, Chazhong Road, Fuzhou, Fujian Province, China. Participants’ legal representative sign an informed consent form before this study. Consent for publication: All results are reported as group-level statistics (e.g., means, standard deviations) and tracing to the person level is not possible. The manuscript does not contain any person’s individual data in any form., (© 2025. The Author(s).)

Background: Data on the predictive value of coronary computed tomography angiography-derived fractional flow reserve (CT-FFR) for long-term outcomes are limited., Methods and Results: A retrospective pooled analysis of individual patient data was performed. Deep-learning-based CT-FFR was calculated. All patients enrolled were followed-up for at least 5 years. The primary outcome was major adverse cardiovascular events. The secondary outcome was death or nonfatal myocardial infarction. Predictive abilities for outcomes were compared among 3 models (model 1, constructed using clinical variables; model 2, model 1+coronary computed tomography angiography-derived anatomical parameters; and model 3, model 2+CT-FFR). A total of 2566 patients (median age, 60 [53-65] years; 56.0% men) with coronary artery disease were included. During a median follow-up time of 2197 (2127-2386) days, 237 patients (9.2%) experienced major adverse cardiovascular events. In multivariable-adjusted Cox models, CT-FFR≤0.80 (hazard ratio [HR], 5.05 [95% CI, 3.64-7.01]; P <0.001) exhibited robust predictive value. The discriminant ability was higher in model 2 than in model 1 (Harrell's C-statistics, 0.79 versus 0.64; P <0.001) and was further promoted by adding CT-FFR to model 3 (Harrell's C-statistics, 0.83 versus 0.79; P <0.001). Net reclassification improvement was 0.264 ( P <0.001) for model 2 beyond model 1. Of note, compared with model 2, model 3 also exhibited improvement (net reclassification improvement=0.085; P =0.001). As for predicting death or nonfatal myocardial infarction, only incorporating CT-FFR into model 3 showed improved reclassification (net reclassification improvement=0.131; P =0.021)., Conclusions: CT-FFR provides strong and incremental prognostic information for predicting long-term outcomes. The combined models incorporating CT-FFR exhibit modest improvement of prediction abilities, which may aid in risk stratification and decision-making.

Interactions between manganese dioxides (MnO 2 ) and dissolved organic matter (DOM) have long been the subject of scientific inquiry. However, the effect of MnO 2 crystallinity on the DOM fate remains unclear. Herein, we comprehensively investigate the adsorption, protection, and mineralization of DOM by MnO 2 with various crystallinities (order of crystallinity: γ-30 < γ-90 < γ-120). The results show that DOM adsorption is positively correlated with the specific surface area (SSA) of MnO 2 ; γ-30 with the largest SSA adsorbs the highest amount of DOM, resulting in DOM protection. However, γ-90 and γ-120 with a smaller SSA could induce the Maillard reaction and thereby promote the formation of geopolymerized organic matter, leading to reduced bioavailability of DOM. Furthermore, the capability of MnO 2 to mineralize DOM decreases in the order γ-120 > γ-90 > γ-30, and it is determined by both Mn 4+ and hydroxyl radical ( · OH) content. In particular, the contribution of radical-based oxidation of · OH to DOM mineralization is 64.8, 47.4, and 23.7% for γ-30, γ-90, and γ-120, respectively. We propose that crystallinity of MnO 2 may have a significant but hitherto unexplored influence on the global carbon cycle over geological time.

Background: The induction of stem cell differentiation to generate intestinal epithelial cells (IECs) with absorptive functions offers significant therapeutic potential for treating conditions such as Crohn's disease, ulcerative colitis, radiation enteritis, and other refractory intestinal epithelial injuries. Human umbilical cord mesenchymal stem cells (hUC-MSCs) are capable of differentiating into functional IEC-like cells., Objective: This study aimed to induce the differentiation of hUC-MSCs into IECs using a conditioned medium co-culture method., Method: A culture medium derived from human IECs was used as the inductive medium to facilitate the differentiation of hUC-MSCs into IECs. The cellular morphology was assessed using inverted microscopy, and the expression of IEC markers, including Villin, CK20, CK8, and CK18 proteins, was analyzed via immunofluorescence staining. Furthermore, the expression levels of IEC markers, such as KRT18, were quantified using real-time quantitative PCR analysis. The functionality of the differentiated IECs in terms of sucrase secretion was assessed through sucrase activity assays., Results: By the 14th day of induction, hUC-MSCs exhibited a morphology similar to IECs and exhibited the expression of IEC markers, including the KRT18 gene and Villin, CK20, CK8, and CK18 proteins. Sucrase activity assays further confirmed that the differentiated cells demonstrated significant sucrase activity., Conclusion: The conditioned medium co-culture method effectively induced the differentiation of hUC-MSCs into functional IECs., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

The network intrusion detection system (NIDS) plays a critical role in maintaining network security. However, traditional NIDS relies on a large volume of samples for training, which exhibits insufficient adaptability in rapidly changing network environments and complex attack methods, especially when facing novel and rare attacks. As attack strategies evolve, there is often a lack of sufficient samples to train models, making it difficult for traditional methods to respond quickly and effectively to new threats. Although existing few-shot network intrusion detection systems have begun to address sample scarcity, these systems often fail to effectively capture long-range dependencies within the network environment due to limited observational scope. To overcome these challenges, this paper proposes a novel elevated few-shot network intrusion detection method based on self-attention mechanisms and iterative refinement. This approach leverages the advantages of self-attention to effectively extract key features from network traffic and capture long-range dependencies. Additionally, the introduction of positional encoding ensures the temporal sequence of traffic is preserved during processing, enhancing the model's ability to capture temporal dynamics. By combining multiple update strategies in meta-learning, the model is initially trained on a general foundation during the training phase, followed by fine-tuning with few-shot data during the testing phase, significantly reducing sample dependency while improving the model's adaptability and prediction accuracy. Experimental results indicate that this method achieved detection rates of 99.90% and 98.23% on the CICIDS2017 and CICIDS2018 datasets, respectively, using only 10 samples., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2025 Xu et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Loading with non-metal cocatalysts to regulate interfacial charge transfer and separation has become a prominent focus in current research. In this study, g-C 3 N 4 /CNT composites loaded with non-metallic cocatalysts were prepared through in situ pyrolysis using urea and CNTs. Various characterization techniques, including transmission electron microscopy (TEM), X-ray diffraction (XRD), X-ray photoelectron spectroscopy (XPS), ultraviolet-visible diffuse reflectance spectroscopy (UV-vis DRS), photoelectrochemical (PEC) analysis, fluorescence lifetime spectroscopy (TRPL), electron paramagnetic resonance spectroscopy (ESR), and photoluminescence (PL) spectroscopy, were employed to analyze the sample's microstructure, phase composition, elemental chemical states, and photoelectronic properties. The photocatalytic performance of the g-C 3 N 4 /CNT composite in the degradation of actual drilling hydraulic filtrate was evaluated under simulated sunlight irradiation, with the degradation results assessed through COD and chroma measurements. The findings indicate that in g-C 3 N 4 /CNT composites loaded with non-metal cocatalysts, the photocatalytic performance improves significantly as the CNT content increases. At a CNT mass fraction of 6.0%, the composite achieves optimal performance, with a COD degradation rate of 0.3742 h -1 and a chroma degradation rate of 81%. These results offer valuable insights into enhancing photocatalytic treatment of waste drilling hydraulic filtrate using g-C 3 N 4 -based non-metallic cocatalysts., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

This paper presents the development and application of attapulgite/polyimide nanofiber composite aerogels (ATP/PI NFAs) integrated with a range of acid-base indicators, fabricated using electrospinning and freeze-drying technologies. A detailed characterization of the ATP/PI NFAs revealed a 3D multi-level pore structure that enhanced the mass transfer of target gas molecules and their interaction with probe molecules. Utilizing machine learning approaches, we designed an ATP/PI NFAs-based colorimetric sensor array capable of real-time evaluation of balsa fish freshness. Color features sensitive to changes in freshness were selected using principal component analysis and random forest. Partial least squares regression and random forest regression models were established, achieving the prediction of total volatile basic nitrogen content in balsa fish. The system was validated using a national standard method to demonstrate its accuracy and practicality. The combination of advanced ATP/PI NFAs-based colorimetric sensor array with robust machine learning models paves the way for food safety monitoring., 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 Ltd.)

Objective: Growing evidence indicates that F-box and leucine-rich repeat protein 6 (FBXL6) is associated with the progression of various cancers, including gastric cancer, hepatocellular carcinoma, and colorectal cancer. This study focuses on the prognostic significance of FBXL6 in OC., Methods: Differential levels of FBXL6 in multiple cancers were evaluated using the TCGA and GSE26712 databases. We screened FBXL6-related differentially expressed genes using the GSE63885 dataset and conducted Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathways analysis. The genes that associate with FBXL6 were screened using the "limma" package, the STRING database, and Cytoscape software, and the association was validated through Gene Expression Profiling Interactive Analysis. The potential substrates of FBXL6 were predicted using UbiBrowser2.0 database. FBXL6 protein levels in 84 OC samples were evaluated using immunohistochemistry. The prognostic significance of FBXL6 was explored using Kaplan-Meier and Cox regression analyses. Based on the Cox regression results, an FBXL6-based nomogram that can predict the overall survival (OS) rate were constructed. Moreover, we examined the net benefits and discriminative ability of the nomogram using the decision curve analysis (DCA), calibration plots, and receiver operating characteristic (ROC) curve., Results: FBXL6 was elevated in OC tissues, and the overexpression of FBXL6 was linked to poor prognosis in OC patients. The ROC and DCA curves indicated that the prognostic value of the FBXL6-based nomogram model was superior to that of FBXL6, age, and FIGO stage alone., Conclusions: Elevated FBXL6 expression was an independent factor for OC, and an easily applied nomogram was developed to predict OS in OC 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 The Author(s). Published by Elsevier B.V. All rights reserved.)

Up to half of hepatocellular carcinoma (HCC) cases are diagnosed at an advanced stage, for which effective treatment options are lacking, resulting in a poor prognosis. Over the past few years, the combination of immune checkpoint inhibitors and anti-angiogenic targeted therapy has proven highly efficacious in treating advanced HCC, significantly extending patients' survival and providing a potential for sequential curative surgery. After sequential curative hepatectomy or liver transplantation following conversion therapy, patients can receive long-term survival benefits. In order to improve the long-term survival rate of the overall population with liver cancer and achieve the goal of a 15% increase in the overall 5-year survival rate outlined in the Healthy China 2030 blueprint, the Professional Committee for Prevention and Control of Hepatobiliary and Pancreatic Diseases of Chinese Preventive Medicine Association, Chinese Society of Liver Cancer, and the Liver Study Group of Surgery Committee of Beijing Medical Association organized in-depth discussions among relevant domestic experts in the field. These discussions focused on the latest progress since the release of the Chinese expert consensus on conversion therapy of immune checkpoint inhibitors combined antiangiogenic targeted drugs for advanced hepatocellular carcinoma (2021 Edition) and resulted in a new consensus on the modifications and supplements to related key points. This consensus aims to further guide clinical practice, standardize medical care, and promote the development of the discipline.

Coastal/offshore renewable energy sources combined with seawater splitting offer an attractive means for large-scale H 2 electrosynthesis in the future. However, designing anodes proves rather challenging, as surface chlorine chemistry must be blocked, particularly at high current densities ( J ). Additionally, waste seawater with increased salinity produced after long-term electrolysis would impair the whole process sustainability. Here, we convert seawater to O 2 selectively, on hydroxides, by building phytate-based expanded negative electrostatic networks (ENENs) with electrostatically repulsive capacities and higher negative charge coverage ranges than those of common inorganic polyatomic anions. With surface ENENs, even typically unstable CoFe hydroxides perform nicely toward alkaline seawater oxidation at activities of >1 A cm -2 . CoFe hydroxides with phytate-based ENENs exhibit prolonged lifespans of 1000 h at J of 1 A cm -2 and 900 h at J of 2 A cm -2 and thus rival the best seawater oxidation anodes. Direct introduction of trace phytates to seawater weakens corrosion tendency on conventional CoFe hydroxides as well, extending the life of hydroxides by ∼28 times at J of 2 A cm -2 . A wide range of materials all obtain prolonged lifetimes in the presence of ENENs, validating universal applicability. Mechanisms are studied using theoretical computations under working conditions and ex situ / in situ characterizations. We demonstrate a potentially viable way to sustainably reutilize high-salinity wastewater, which is a long-standing but neglected issue. Series-connected devices exhibit good resistance to low temperature operation and are more eco-friendly than current organic electrolyte-based energy storage devices.

The discontinuous fiber reinforced hydrogels are easy to fail due to the fracture of the fiber matrix during load-bearing. Here, we propose a novel strategy based on the synergistic reinforcement of interconnected natural fiber networks at multiple scales to fabricate hydrogels with extraordinary mechanical properties. Specifically, the P(AA-AM)/Cel (P(AA-AM), poly(acrylic acid-acrylamide); Cel, cellulose) hydrogel is synthesized by copolymerizing AA and AM on a substrate of paper with an interconnected hollow cellulose microfiber network. This innovative design achieves a collaborative improvement of mechanical properties, including a 253-times increase in strength (27.8 vs. 0.11 MPa), 137-times increase in work of fracture (3.59 vs. 0.026 MJ m -3 ), and 235-times increase in fracture energy (16.48 vs. 0.07 kJ m -2 ). These outstanding mechanical properties benefit from the P(AA-AM) network formed by the copolymerization, which fills both the inside and outside of the hollow cellulose fibers, thus establishing abundant strong hydrogen bonds with the fibers and welding the fiber junctions. Consequently, the hydrogel exhibits enhanced resistance to the slippage and fracture of fibers. This strategy demonstrates the mechanical strengthening effectiveness of a variety of hydrogels by regulating the water-cellulose-copolymer interplay, representing a practical and universal route for designing super-strong hydrogels., (Copyright © 2025. Published by Elsevier B.V.)

Background: Although previous studies have investigated the risk factors for rotator cuff syndrome (RCS), there remains controversy due to uncontrolled and uncertain confounding factors in their analyses., Purpose: To perform Mendelian randomization (MR) analysis using single-nucleotide polymorphisms to investigate the causal relationship between RCS and 4 risk factors: type 2 diabetes mellitus (T2DM), high blood pressure (HBP), body mass index (BMI), and low high-density lipoprotein cholesterol (HDL-C)., Study Design: Descriptive epidemiology study., Methods: Genome-wide association study (GWAS) data for T2DM (ebi-a-GCST006867), BMI (ieu-b-40), HBP (finn-b-I9&#95;HYPTENS), HDL-C (ieu-b-109), and RCS (ukb-b-50) were obtained from the IEU Open GWAS Project. The dataset of each risk factor was combined with the dataset of RCS, generating 4 datasets. Potential confounders and single-nucleotide polymorphisms related to RCS were excluded from these datasets. The causal relationships between the exposure factors and RCS were analyzed using 5 regression models: MR-Egger, weighted median estimate (WME), inverse-variance weighting (IVW), simple mode, and weighted mode. Heterogeneity in the causal effects was assessed using MR-Egger regression and IVW analyses. Sensitivity analyses were performed to determine the stability of the results., Results: The MR-Egger regression intercepts for T2DM, BMI, HBP, and HDL-C showed no horizontal pleiotropic effects. The results of the Cochran Q test showed P values of .075 and .080 for BMI in the MR-Egger regression and IVW models, respectively, indicating the absence of heterogeneity between BMI and RCS. The results of the weighted median estimate and IVW regression analyses showed a significant causal association between BMI and RCS, with odds ratios of 1.002 (95% CI, 1-1.004; P = .038) and 1.003 (95% CI, 1.001-1.005; P = .0003), respectively. No significant associations were found for T2DM, HDL-C, or HBP., Conclusion: In the present study, BMI was positively associated with the risk of developing RCS, while T2DM, HBP, and low HDL-C were not associated with RCS development., Competing Interests: The authors have declared that there are no conflicts of interest in the authorship and publication of this contribution. AOSSM checks author disclosures against the Open Payments Database (OPD). AOSSM has not conducted an independent investigation on the OPD and disclaims any liability or responsibility relating thereto., (© The Author(s) 2025.)

The rising prevalence of multidrug-resistant (MDR) Gram-positive bacteria threatens the effectiveness of current antibiotic therapies. However, the development of new antibiotics has stagnated in recent years, highlighted the critical need for the discovery of innovative antimicrobial agents. This study aims to evaluate the antibacterial activity of naphthoquinones derived from Arnebia euchroma (Royle) Johnst (ADNs) and elucidate their underlying mechanisms. The antibacterial efficacy of ADNs was assessed using the microbroth dilution method. The antibacterial mechanism of acetylshikonin (ASK) was further explored through scanning electron microscopy, RNA-Seq and transcriptomic analysis, fluorescent probes, high-performance liquid chromatography, qRT-PCR and molecular docking. The results demonstrated that all the ADNs exhibit potent antibacterial activity against MDR Gram-positive pathogens, including methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant Enterococcus, and linezolid-resistant Enterococcus. Notably, ASK showed minimum inhibitory concentration of 1-2 μg/mL against MRSA. Mechanistic investigations revealed that ASK operates through a multifaceted antibacterial mechanism. First, ASK disrupts bacterial membrane integrity and dissipates proton motive force by targeting membrane phospholipids. Further analysis demonstrated a significant reduction in oxygen consumption and ATP production, indicative of respiratory chain inhibition. Additionally, ASK interferes with bacterial cell wall synthesis, as evidenced by reduction of peptidoglycan precursors and downregulated expression of genes involved in peptidoglycan synthesis. In conclusion, ASK represents a promising antimicrobial agent with potential efficacy against infections caused by MDR Gram-positive bacteria and offers valuable insights for the development of novel therapeutic strategies., (© 2024 John Wiley & Sons Ltd.)

Introduction: Salmonella, a foodborne zoonotic pathogen, is a significant cause of morbidity and mortality in animals and humans globally. With the prevalence of multidrug-resistant strains, Salmonellosis has become a formidable challenge. Host-directed therapy (HDT) has recently emerged as a promising anti-infective approach for treating intracellular bacterial infections., Objectives: Plant-derived natural products, owing to their structural and functional diversity, are increasingly being explored and utilized as encouraging candidates for HDT compounds. This study aims to identify and screen natural compounds with potential as HDT for the treatment of intracellular Salmonella infections., Methods: A cell-based screening approach was deployed to identify natural compounds capable of mitigating the intracellular replication of S. enterica. Safety and efficacy of the candidate compounds were evaluated using multiple animal models. RNA sequencing, ELISA, and immunoblotting analyses were conducted to elucidate the underlying mechanisms of action., Results: Our results reveal that fangchinoline (FAN) effectively reduces S. enterica survival both in vitro and in vivo. Meanwhile, FAN also displays anti-infective activity against other intracellular pathogens, including multidrug-resistant isolates. A 14-day safety evaluation in mice showed no significant toxic or adverse effects from FAN administration. RNA sequencing analysis reveals an upregulation of lysosome pathways in S. enterica-infected cells treated with FAN. Mechanistic studies indicate that FAN increases acid lysosomal quantities and fosters autophagic response in Salmonella-infected cells via the AMPK-mTORC1-TFEB axis. In addition, FAN alleviates the inflammatory response in Salmonella-infected cells by inactivating the NF-κB pathway., Conclusion: Our findings suggest that FAN represents a lead HDT compound for tackling recalcitrant infections caused by intracellular bacterial pathogens., 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. Published by Elsevier B.V.)

Tigecycline is a last-resort antibiotic to treat complicated infections caused by multidrug-resistant pathogens, while the emergence of plasmid-mediated tet(X) family severely compromises its clinical efficacy. Novel antimicrobial strategies not limited to new antibiotics in pharmaceutical pipeline are urgently needed. Herein, we reveal the metabolic disparities between tet(X)-negative and -positive E. coli, including distinct energy demand patterns under tigecycline exposure. In particular, the cysteine and methionine metabolism pathway is remarkably downregulated in tet(X)-positive bacteria. More importantly, we find that the addition of exogenous L-methionine (Met) effectively resensitizes tet(X)-positive pathogens to tigecycline. Our mechanistic analysis demonstrates that exogenous Met promotes intracellular tigecycline accumulation by upregulating bacterial proton motive force. Moreover, Met accelerates the conversion to S-adenosyl-L-methionine, an essential methyl donor, thereby enhancing 5mC methylation modification in the promoter region of tet(X4) gene and reducing its expression. Consistently, the potentiation of Met to tigecycline is abolished in tet(X4)-carrying E. coli Δdcm but restored in dcm-complementary bacteria, which encodes DNA-cytosine methyltransferase. In multiple animal models of infection, Met markedly potentiates the effectiveness of tigecycline against pathogenic E. coli and K. pneumoniae. Overall, this work highlights the therapeutic potential of Met in overcoming plasmid-mediated high-level tigecycline resistance, and provides a new paradigm to enhance antibiotic efficacy by harnessing cellular metabolic networks as well as epigenetic modifications., Competing Interests: Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Background: Male pattern baldness (MPB) is commonly associated with prostate diseases, both of which can significantly impact men's quality of life. However, the relationship and causality between them remain unclear. In this study, we investigated the causal relationship between the two., Methods: Inverse variance weighting (IVW) was the primary Mendelian randomization method, with MR Egger, weighted median, and MRPRESSO as complements. Sensitivity analyses included Cochran's Q, MR Egger intercept, and MRPRESSO., Results: MPB was found to be negatively correlated with prostate cancer (IVW: OR = 0.986, 95% CI = 0.974-0.999, P = 0.033). This causal relationship was further supported by the weighted median (OR = 0.981, 95% CI = 0.969-0.993, P = 0.002), MR-Egger (OR = 0.977, 95% CI = 0.960-0.994, P = 0.010), and MRPRESSO (OR = 0.986, 95% CI = 0.974-0.999, P = 0.037) methods. Additionally, the weighted median analysis indicated that MPB was positively correlated with benign prostatic hyperplasia (BPH) (OR = 1.027, 95% CI = 1.003-1.052, P = 0.024)., Conclusions: Our findings suggest that genetically predicted MPB may reduce prostate cancer risk but increase the risk of benign prostatic hyperplasia. Timely prostate screening in patients with MPB could help prevent and manage prostate diseases., Competing Interests: Declarations. Ethics approval and consent to participate: Not applicable to this study. Consent for publication: Not applicable to this study. Conflict of interest: There is no conflict of interest to declare., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

A novel gold nanocluster surface molecularly imprinted polyisopropylacrylamide probe (AuNC@MIP) was synthesized for the specific detection of NO 2 - , using N-isopropylacrylamide (NIPAM) as the functional monomer, gold nanoclusters (AuNC) as the substrate, ethylene glycol dimethacrylate (EGDMA) as the cross-linking agent, and nitrosophenol (NPN) produced from sodium nitrite (NaNO 2 ) and phenol (PN) as the template molecule, N,N-dimethylformamide (DMF) as the solvent, and azobisisobutyronitrile (AIBN) as the initiator. The nanoprobe was characterized using molecular spectroscopy, XPS, TEM, TGA, and zeta potential analysis. The probes revealed a prominent resonance Rayleigh scattering (RRS) peak at 370 nm. Upon addition of NO 2 - , the RRS intensity at 370 nm decreased due to the RRS energy transfer enhancing. The linear determination range is 0.125-1.50 nmol/L NO 2 - , with a limit of detection (LOD) of 0.085 nmol/L. The new RRS method was applied to determine NO 2 - in meat, dairy products, and water samples, with recovery of 96-107% also relative standard deviations (RSDs) of 1.1-8.0%., Competing Interests: Declarations. Competing interests: The authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH, DE part of Springer Nature.)

Objectives: Tigecycline, a last-resort antibiotic in the tetracycline class, has been effective in treating infections caused by multidrug-resistant bacteria. However, the emergence of the tigecycline resistance gene cluster tmexCD-toprJ, which encodes a resistance-nodulation-division efflux pump, has significantly limited its therapeutic effectiveness. This study aims to explore the potential of CRISPR/Cas9-based plasmids to target and cleave tmexCD-toprJ gene cluster from bacterial plasmids and chromosomal integrative conjugative elements (ICEs), respectively., Methods: We developed two CRISPR/Cas9-based plasmids, pCas9Kill and pCas9KillTS. The pCas9Kill plasmid designed to eliminate tmexCD-toprJ from plasmids through electroporation, while the pCas9KillTS plasmid, delivered through conjugation, targeted tmexCD-toprJ within ICEs on the bacterial chromosome. The plasmid modifications were assessed using nanopore long-read sequencing., Results: Electroporation with the pCas9Kill plasmid resulted in the removal of tmexCD-toprJ from plasmids, restoring bacterial susceptibility to tigecycline. Nanopore sequencing revealed that the plasmids were repaired by insertion sequences after tmexCD-toprJ removal. In contrast, the pCas9KillTS plasmid introduced via conjugation to target tmexCD-toprJ gene cluster on ICEs within the chromosome. This approach led to chromosomal cleavage and subsequent bacterial cell death., Conclusion: Our results demonstrate that both plasmids effectively inactivated tmexCD-toprJ, with pCas9Kill restoring tigecycline susceptibility in plasmid-bearing strains and pCas9KillTS causing targeted cell death in chromosomal ICE-harbouring bacteria. This study highlights the potential of CRISPR/Cas9 systems in addressing antibiotic resistance, providing a promising strategy to combat tigecycline-resistant pathogens., (Copyright © 2024 Elsevier Ltd and International Society of Antimicrobial Chemotherapy. All rights reserved.)

Late-onset Pompe disease (LOPD) is caused by a genetic deficiency of the lysosomal enzyme acid alpha-glucosidase (GAA), leading to progressive limb-girdle weakness and respiratory impairment. The insidious onset of non-specific early symptoms often prohibits timely diagnosis. This study aimed to validate the high-risk screening criteria for LOPD in the Chinese population. A total of 726 patients were included, including 96 patients under 14 years of age. Dried blood spots (DBS) and tandem mass spectrometry (MS/MS) were employed to evaluate serum GAA activity. Forty-four patients exhibited a decreased GAA activity, 16 (2.2%) of which were confirmed as LOPD by genetic testing. Three previously unreported GAA mutations were also identified. The median diagnostic delay was shortened to 3 years, which excelled the previous retrospective studies. At diagnosis, most patients exhibited impaired respiratory function and/or limb-girdle weakness. Elevated serum creatine kinase (CK) levels were more frequently observed in patients who manifested before age 16. Overall, high-risk screening is a feasible and efficient method to identify LOPD patients at an early stage. Patients over 1 year of age with either weakness in axial and/or proximal limb muscles, or unexplained respiratory distress shall be subject to GAA enzymatic test, while CK levels above 2 times the upper normal limit shall be an additional criterion for patients under 16. This modified high-risk screening criteria for LOPD requires further validation in larger Chinese cohorts., (© 2024 SSIEM.)

Objective: Repetitive transcranial magnetic stimulation (rTMS) to the left dorsolateral prefrontal cortex (L-DLPFC) has an improving effect in cognitive function, but it is still not clear in what specific cognitive domains. We here combined a single session of TMS (HF-rTMS/iTBS) with electroencephalography (EEG) to clarify the effects of magnetic stimulation techniques on executive function, working memory, and visuospatial attention in healthy participants, and to investigate the underlying neurophysiological mechanisms., Methods: Fifty-one healthy participants were randomly assigned to three stimulation groups (HF-rTMS, iTBS, and sham groups). Classical psychological paradigms (task-switching, 2-back with visual Oddball) and event-related potentials (ERPs) were performed to compare the behavioral indices of each paradigm before and after the two stimulations, as well as the changes in the ERP components., Results: Analysis of behavioral indicators showed that reaction times in the 2-back paradigm were faster after HF-rTMS and iTBS than after sham stimulation. However, no statistically significant differences were observed in the behavioral changes in the task-switching and visual Oddball paradigms. ERP analysis showed that N2 amplitude in the frontal and central regions of the participants increased during the 2-back paradigm following HF-rTMS and iTBS; however, no statistically significant differences were observed between the ERP components of the task-switching and visual Oddball paradigms., Conclusion: Single sessions of HF-rTMS and iTBS on the L-DLPFC specifically enhanced working memory performance, with no significant effects on executive function and visuospatial attention. Both true stimulations elicited more negative N2 in the frontal and central channels during the 2-back paradigm, suggesting increased recruitment of cognitive resources from these brain areas. Although iTBS and HF-rTMS improved working memory behavior, iTBS's shorter stimulation time suggests it may have greater potential for clinical applications in terms of time-benefit costs., Competing Interests: Declaration of Competing Interest We declare that we have no financial and personal relationships with other people or organizations that can inappropriately influence our work, there is no professional or other personal interest of any nature or kind in any product, service and / or company that could be construed as influencing the position presented in, or the review of, the manuscript entitled," Single High-Frequency Repetitive Transcranial Magnetic Stimulation and Intermittent Theta Pulse Stimulation Both Promote Working Memory Behavior in Participants: An Event-Related Potential Study "., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

The pathogenesis of alcohol-associated liver disease (ALD) is complex, and involving ethanol-induced enhancement of gut permeability results in the release of bacterial products from the intestine. This triggers intrahepatic inflammation and liver damage, with hepatic macrophages playing key roles in the inflammatory response to alcohol. Sirtuin 7 (SIRT7), an NAD + -dependent type III histone deacetylase, is being recognized as a potential therapeutic target in various human diseases, including cancer. Emerging evidence shows that SIRT7 participates in immune regulation, but whether it is involved in ALD remains elusive. In the present study, using myeloid cell-specific Sirt7 knockout mice (Lyz2-Sirt7 -/- ), we observed that knockout Sirt7 in myeloid cells significantly ameliorated alcohol-induced liver injury, inflammation, and cell infiltration, while only mildly affecting lipid metabolism pathways. We further identified chemokine (C-C motif) ligand 2 (CCL2) as the main target impaired by Sirt7 knockout after alcohol. In vitro studies confirmed that Sirt7 knockout impaired macrophages' ability of CCL2 secretion and monocyte recruiting, and exogenous CCL2 reversed this impairment. At the molecular level, we found that knockout of Sirt7 significantly impaired lipopolysaccharide-induced p65 phosphorylation and nuclear localization. More importantly, the SIRT7 inhibitor 40569 sufficiently decreased alcohol-induced liver injury and hepatic inflammation via preventing CCL2 in vivo. Our data thus uncover a previously undescribed role of myeloid SIRT7 in mediating ALD via promoting CCL2 secretion through the NF-κB signaling pathway. Targeting SIRT7 might offer novel mechanism-based therapeutic options for ALD., Competing Interests: Disclosure Statement None declared., (Copyright © 2025. Published by Elsevier Inc.)

Background: Early detection for colorectal cancer (CRC) can enhance the patient prognosis. We aimed to validate the combined multi-gene detection in plasma of Septin9 , SDC2 , KCNQ5 , and IKZF1 for early diagnosing of CRC in this prospective study., Methods: Overall, 124 participants including 45 CRC patients, 8 advanced adenoma patients, 34 small polyp patients, and 37 normal controls who underwent colonoscopy were enrolled. The carcinoembryonic antigen (CEA) test and methylation tests for Septin9 , SDC2 , KCNQ5 , and IKZF1 were performed. Sensitivity, specificity, and the area under the curve (AUC) of the receiver operating characteristic (ROC) curve were utilized to evaluate the diagnostic value of each biomarker. Additionally, the association between the positive rates of methylated Septin9 , SDC2 , KCNQ5 , and IKZF1 and the clinicopathological characteristics of CRC was also analyzed., Results: The positive detection rate of multi-gene methylation in CRC patients was 86.67%, for stage I and stage II patients, the positive rates were 90.91% and 87.50%, both of which were significantly higher than CEA, which had rates of 55.56%, 18.18% and 56.25% for the corresponding stages. In patients with advanced adenomas and small polyps, the positive rates for the four-gene combined test were 62.50% and 52.94%, respectively, which were markedly higher than the CEA rates of 12.50% and 14.71%. AUC of the ROC curve indicated that the diagnostic value of the multi-gene test for CRC was superior to that of any single gene. Correlation analysis revealed that the positive rate of the test was not affected by patients' clinicopathological characteristics., Conclusions: A combination of methylated Septin9 , SDC2 , KCNQ5 , and IKZF1 test has the potential for early diagnosis of CRC patients, advanced adenoma patients, and small polyp patients., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://tcr.amegroups.com/article/view/10.21037/tcr-24-729/coif). Y.X. and X.L. are employees of Molecular Diagnostic Engineering Technology Research Center of Zhengzhou. The other authors have no conflicts of interest to declare., (2024 AME Publishing Company. All rights reserved.)

DNA methylation is an epigenetic modification process that can alter the functionality of a genome. It has been reported to be a key regulator of fruit ripening. In this study, the DNA methylation changes of CpG islands of ethylene signaling genes regulated by 1-methylcyclopropene (1-MCP) during ripening and senescence of tomato fruit were detected. The results showed that the 1-MCP treatment decreased the accumulation of lycopene, maintained the content of vitamin C, and delayed the ripening and senescence of tomato fruit. The quantitative real-time PCR and bisulfite sequencing analysis showed that 1-MCP treatment changed the expression and the DNA methylation level of CpG islands related to the ethylene signaling pathway genes, among which the DNA methylation change of LeEIN3 was the most significant. Compared with the control, 1-MCP treatment increased the DNA methylation level of the CpG island of the LeEIN3 gene, reduced the expression of LeEIN3 in tomato fruit, and was involved in 1-MCP delaying the postharvest senescence of tomato fruit. The results indicated that DNA methylation changes of ethylene signaling genes were involved in ethylene synthesis and signal transduction and played an important role in the regulation of 1-methylcyclopropene, delaying postharvest ripening and senescence of tomato fruit.

The emergence and dissemination of tigecyline resistant Enterobacterales (TRE) in animals is a critical issue. This study aimed to investigate the presence of TRE in the gut of healthy avians as well as meat samples. A total of 940 ceacal samples from 94 commercial poultry flocks were collected at slaughter and a total of 335 meat samples [(chicken (n = 159), turkey (n = 4) and beef/lamb (n = 172)] were collected from supermarkets and butcher shops. Out of 960 samples, 146 (19.21 %) samples from chicken farms and 24 (13.3 %) from turkey farms were positive for TRE. Forty-nine Escherichia coli isolates were determined to carry the tet(X4) gene by PCR and exhibited multi-drug resistance. Whole-genome short-read sequencing (WGS) on all tet(X4) positive E. coli isolates and long-read sequencing on a selection of five isolates were carried out. WGS identified four ST types (ST206 being the most dominant, ST609, ST744 and ST189), indicating significant homogeneity among tigecyline resistant E. coli strains. In 47 isolates, the tet(X4) gene was transferrable to E. coli EC600 and it was found to be located on the IncX1 plasmid. Additionally, all tet(X4)-positive E. coli isolates also harbored other resistance genes, including floR, aadA2 and tet(A). In this study, the identification of tet(X4) carrying E. coli in healthy chicken and meats suggests the likely source of food-producing animals for humans. Therefore, active surveillance of critical priority lineages of TRE should focus on to contain the potential public health risk., Competing Interests: Declaration of competing interest The authors certify that they have NO affiliations with or involvement in any organization or entity with any financial interest (such as honoraria; educational grants; participation in speakers’ bureaus; membership, employment, consultancies, stock ownership, or other equity interest; and expert testimony or patent-licensing arrangements), or non-financial interest (such as personal or professional relationships, affiliations, knowledge or beliefs) in the subject matter or materials discussed in this manuscript., (Copyright © 2024. Published by Elsevier Inc.)

The sluggish kinetics of the anodic process, known as the oxygen evolution reaction (OER), has posed a significant challenge for the practical application of proton exchange membrane water electrolyzers in industrial settings. This study introduces a high-performance OER catalyst by anchoring iridium oxide nanoparticles (IrO 2 ) onto a cobalt oxide (Co 3 O 4 ) substrate via a two-step combustion method. The resulting IrO 2 @Co 3 O 4 catalyst demonstrates a significant enhancement in both catalytic activity and stability in acidic environments. Notably, the overpotential required to attain a current density of 10 mA cm -2 , a commonly used benchmark for comparison, is merely 301 mV. Furthermore, stability is maintained over a duration of 80 h, as confirmed by the minimal rise in overpotential. Energy spectrum characterizations and experimental results reveal that the generation of OER-active Ir 3+ species on the IrO 2 @Co 3 O 4 surface is induced by the strong interaction between IrO 2 and Co 3 O 4 . Theoretical calculations further indicate that IrO 2 sites loaded onto Co 3 O 4 have a lower energy barrier for *OOH deprotonation to form desorbed O 2 . Moreover, this interaction also stabilizes the iridium active sites by maintaining their chemical state, leading to superior long-term stability. These insights could significantly impact the strategies for designing and synthesizing more efficient OER electrocatalysts for broader industrial application.

The establishment and maintenance of spermatogenesis is a complex process involving a vast of regulatory pathways. There is growing evidence revealing that long noncoding RNAs (lncRNA) play important roles in regulating testicular development and spermatogenesis in a stage-specific way. However, our understanding of how lncRNA regulates testicular development and spermatogenesis in black goats is quite limited. In the current study, we screened the transcriptomes (lncRNA and mRNA) of testicular from Guangxi black goats before puberty (3 days old, D3; 30 days old, D30), puberty (90 days old, D90) and postpuberty (180 days old, D180), in order to identify the lncRNA interaction with mRNAs contributes to goat spermatogenesis. The RNA-sequencing (RNA-seq) analysis showed that there were 1211, 12,180, 834 differential lncRNAs and 1196, 8838,269 differential mRNAs at the ages of D30 vs. D3, D90 vs. D30, and D180 vs. D90. The lncRNAs showed the most significantly changes from D30 to D90, which indicated that D90 was a key node of lncRNAs participated in the regulation of testicular development and spermatogenesis in black goat. According to functional enrichment analysis of GO and KEGG, we found that differentially expressed lncRNAs (DE lncRNAs) and their target genes regulated spermatogenesis through signal pathways including MAPK, Ras, and PI3K-Akt. Using cis- and trans-acting, 39 DE lncRNAs-targeted genes were found to be enriched for male reproduction. Of these, LOC108635509, which specific expressed in testis and upregulated the expression levels at D90, was found participated in the regulation of testicular development through promoting the proliferation of Sertoli cells (SCs). Overall, this study provides new insight into the regulatory mechanisms that support spermatogenesis and testicular development in black goats., Competing Interests: Declarations. Ethics approval and consent to participate: All experiments were approved by the Animal Care and Use Committee of Guangxi University, China (NO. GXU-2023-0210). The animals used in the present study were permitted and provided by Guangxi Green World Moyang Breeding Base, Nanning, China. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

2-Methylquinazolin-4(3 H )-ones were efficiently constructed using solid calcium carbide as an alkyne source, 2-aminobenzamides or 2-aminobenzohydrazides as substrates, and p -tolylsulfonyl azide as a mediator through simultaneous formation of two C-N bonds in one step. The salient features of this protocol are the use of an inexpensive, abundant and easy-to-use alkyne source as a substitute for flammable and explosive gaseous acetylene, low-cost catalyst, wide substrate scope, satisfactory yield, and simple manipulation. This method can also be extended to gram scale.