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Restoring motor function and preventing re-rupture and adhesion during Achilles tendon healing remain significant clinical challenges. Increasing evidence suggests that miRNA plays a crucial role in tendon healing and regeneration. The previously designed nanosphere hydrogel sustained-release system enables targeted, controlled release of drugs. In this study, we developed a version of this system loaded with miR-34a-5p for localized delivery to an acute Achilles tendon injury model. The results of the Achilles functional index and Catwalk behavior analysis in rats indicated that miR-34a-5p mimic promoted early recovery of motor function following Achilles tendon injury. Although gross observation suggested that the miR-34a-5p mimic group had a minimal inhibitory effect on the adhesion of Achilles tendon tissue, tension analysis demonstrated that it effectively increased the maximum tensile strength. Additionally, in vitro experiments showed that miR-34a-5p mimic could increase tendon cells proliferation and improve tendon cells viability. This study confirmed the efficacy of the miR-34a-5p nanosphere hydrogel sustained-release system in tendon injury repair, presenting it as a promising treatment strategy for clinical practice., Competing Interests: Declaration of competing interest The authors declare that they have no conflicts of interest., (Copyright © 2024. Published by Elsevier Ltd.)

Tuberculosis drug resistance contributes to the spread of tuberculosis. Immunotherapy is an effective strategy for treating tuberculosis, with the regulation of macrophage-mediated anti-tuberculosis immunity being crucial. Norcantharidin (NCTD), a drug used in tumor immunotherapy, has significant immunomodulatory effects. Thus, NCTD may have an anti-tuberculosis role by regulating immunity. Understanding how NCTD affects the proteome of Mtb-infected macrophages can provide valuable insights into potential treatments. This study aimed to investigate the impact of NCTD (10 μg/mL) on the proteome of macrophages infected with Mtb H37Ra using liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis. A total of 69 differentially regulated proteins (DRPs) were identified, with 28 up-regulated and 41 down-regulated in the NCTD-treated group. Validation of six DRPs (CLTCL1, VAV1, SP1, TRIM24, MYO1G, and WDR70) by Western blot analysis confirmed the accuracy of the LC-MS/MS method used in this study. NCTD modulates various protein expressions involved in chromatin-modifying enzymes, RHO GTPases activating PAKs, Fc gamma R-mediated phagocytosis, T cell receptor signaling pathway, and antigen processing and presentation. Overall, the research provides new insights into the effects of NCTD on the proteome of Mtb-infected macrophages. The identified changes highlight potential targets for future therapeutic interventions aimed at enhancing host immunity against Mtb infection or developing new anti-TB drugs based on these findings., Competing Interests: Declarations. Ethics approval and consent to participate: This study does not entail experiments involving human or animal subjects. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Hetero-metal doping or substitution to create alloy clusters is a highly appealing strategy for improving physicochemical characteristics as well as tailoring optical and electronic properties, although high-yield synthesis of alloy clusters with precise positioning of doped metals is a daunting challenge. Herein, we manifest rational synthesis of chiral alloy cluster enantiomers R/S-Ag6Cu in 85%-87% yield by replacing one Ag(I) atom with Cu(I) in homometallic clusters R/S-Ag7, achieving circularly polarized luminescence (CPL) with a quantum yield beyond 90%. As a small energy gap (ca. 0.07 eV) between S1 and T1 states facilitates thermally activated delay fluorescence (TADF) through reverse intersystem crossing (RISC), the photoluminescence (PL) of R/S-Ag7 and R/S-Ag6Cu at ambient temperature originates mostly from TADF (85% and 86%) in place of phosphorescence (15% and 14%). Relative to those of R/S-Ag7, copper(I) doping not only triples PL quantum yields of R/S-Ag6Cu due to accelerating intersystem crossing and RISC, but also doubles CPL asymmetry factors of R/S-Ag6Cu ascribed to rigidizing cluster structure through stronger Ag-Cu interaction apart from dramatically improving thermodynamic stability. Solution-processable circularly polarized organic light-emitting diodes (CP-OLEDs) demonstrate circularly polarized electroluminescence (CPEL) with external quantum efficiency (EQE) of 26.7%, which is superior to most of red-emitting OLEDs through solution process., (© 2024 Wiley‐VCH GmbH.)

Secondary zinc oxide dust is rich in high-grade metals such as Zn, In, Pb, and Ga, and in the face of the depletion of ore resources at home and abroad, it is of great significance to seek an efficient process to realize the full resource recovery of valuable metals in secondary zinc oxide dust. In this study, on the basis of the thermodynamic analysis of the wet treatment process, three wet treatment methods, namely "low acid leaching", "high acid leaching" and "chlorination leaching", were used to explore the suitable parameters for stepwise extraction of Zn, In and Pb metals. The results showed that the three wet treatment methods could effectively extract the corresponding main elements, and the optimal leaching rates of Zn, In and Pb were 73, 90 and 94%, respectively. Thermodynamic analysis shows that under ideal conditions, the "cascade separation" of some or all metals can be theoretically achieved by using a suitable leaching solvent for zinc oxide dust. The concentration of sulfuric acid, the ratio of liquid solid volume to mass and temperature had great effects on the leaching rate of Zn and In, and the leaching rate of Zn and In also increased with the increase of the values of the three experimental parameters, which was positively correlated. The leaching rate of Pb will increase with the increase of sulfuric acid concentration, but when the pH of the solution system is < 2, Pb will form PbSO 4 precipitate, which inhibits the leaching ability of Pb. In the chlorinated leaching system with "ammonium chloride + hydrochloric acid" as the leaching solvent, the excess Cl - and Pb 2+ fully coordinated to promote the efficient leaching of Pb metal, and the initial pH value of the solution had a great influence on the Leaching Rate of Pb. The multi-stage combined wet treatment process is an effective solution to realize the full quantitative recovery of valuable elements in Secondary zinc oxide dust, In this paper, the suitable process conditions for stepwise extraction of Zn, In and Pb metals were obtained through wet treatment experiments, and the cascade separation of metals in zinc oxide dust was preliminarily realized, which provided an important idea for the efficient utilization of metallurgical dust and sludge solid wastes, and at the same time provided theoretical support for the industrial practice of recycling valuable elements in metallurgical dust., Competing Interests: Declarations. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Objective: To construct and validate a new thyroid imaging reporting and data system (TI-RADS) based on radiating blood flow and grayscale US features., Materials and Methods: This study enrolled patients from 4 hospitals from January 2018 to November 2023 retrospectively and prospectively. All US features associated with malignant thyroid nodules were assessed by multivariable logistic regression to construct baseline US TI-RADS (BUS TI-RADS), which was tested with internal validation set, external validation set and prospective validation set. Additionally, its potential of reducing biopsy was assessed., Results: There were 2932 patients (2153 female, age: 42.83 ± 11.71; 779 male, age: 42.36 ± 11.78) with 3940 nodules (2831 malignant nodules and 1109 benign nodules). Independent predictive factors included composition, echogenicity, shape, margin, suspicious extrathyroidal extension, punctate echogenic foci, and radiating blood flow. Compared with American College of Radiology (ACR) TI-RADS and Chinese TI-RADS (C-TIRADS), the BUS TI-RADS had higher AUCs of 0.96 (95 % CI: [0.95, 0.97]; P < 0.001), 0.93 ([0.90, 0.97]; P < 0.001), 0.91 ([0.86, 0.96]; P < 0.003) and 0.95 ([0.93, 0.97]; P < 0.001) for the training set, internal validation set, external validation set and prospective validation set respectively. Decision curve analysis demonstrated higher net benefit for the BUS TI-RADS. And the BUS TI-RADS (4.1 %; 18.1 %) had lower percentage of biopsy and false negative rate compared with the ACR TI-RADS (31.2 %; 20.9 %) and C-TIRADS(33.1 %; 58.5 %)., Conclusion: BUS TI-RADS was created according to the simplified regression coefficients of radiating blood flow and grayscale ultrasonography features with excellent diagnostic performance and could reduce unnecessary biopsy with lower missed malignancy., 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.)

Although much progress has been made in chemotherapy or target therapy for advanced gastric cancer, the prognosis is still poor. It is necessary to screen biomarkers for early diagnosis and prognosis prediction. However, the prognostic value of LOX family in gastric cancer and the underlying molecular mechanisms for promoting the progression of gastric cancer remains unclear. Among five members of LOX family, LOXL1 was the unique independent prognostic risk factor. The nomogram established based on the expression of LOXL1 and other clinical parameters could predict the overall survival rate of gastric cancer. Knockdown (KD) of LOXL1 decreased cell proliferation and led to G1 phase arrest in gastric cells. According to GSEA analysis that LOXL1 was positively correlated with the WNT signaling pathway, in vitro experiment proved that LOXL1-KD reduced the phosphorylation level of β-catenin and the expression of the downstream G1 phase checkpoint CCND1. In conclusion, LOXL1 has been identified as a potential risk prognostic biomarker for gastric cancer by promoting gastric cancer proliferation via WNT/β-catenin/cyclinD1 pathway., Competing Interests: Declaration of competing interest The authors declare that they have no competing interests or potential competing interests, and all authors should confirm its accuracy., (Copyright © 2024. Published by Elsevier Inc.)

Natural lutein is liposoluble and has powerful antioxidant activity, which can be self-aggregated to form H-type aggregates in organic-water systems. However，its application is limited by poor solubility and high instability. Here, whey proteins/chitosan-coated H-type aggregates lutein nanoparticles (NPs) were fabricated via a bottom-up layer-by-layer self-assembly technique. The optimal conditions for the preparation of the NPs (173.3 nm) were determined by the Dynamic Light Scattering and UV-vis spectroscopy. Briefly, three proteins (WPI and WPC and BSA) were used to fabricate polysaccharide-protein nanocarriers to encapsulate the lutein. These spectroscopy studies indicated that chitosan and BSA formed hydrophobic microdomain by the intermolecular electrostatic attraction force with remarkable changes of secondary structure in protein. The morphology revealed that the NPs were nearly spherical. The EE of the NPs was ≥90.4 %, with a LC of up to 28.3 %. Lutein in NPs can be stabilized as H-type aggregates at different temperatures and pH-values. Additionally, the cytotoxicity test of the NPs on L929 and Caco-2 cells showed that NPs had low cytotoxicity in a limited concentration range. Results indicated that whey protein/chitosan-coated lutein nanoparticles significantly improved water dispersion and stability of lutein and its aggregates, thus broadening their application in nutrient delivery system., 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.)

Purpose: This study investigated the molecular mechanism of quercetin in the treatment of sepsis using network pharmacological prediction and experimentation., Methods: Hub genes were identified by intersecting the differentially expressed genes (DEGs) of the GSE131761 and GSE9960 databases with genes from the hub modules of Weighted Gene Co-Expression Network Analysis (WGCNA), targets of quercetin, and ferroptosis. Subsequently, in order to determine the functional characteristics and molecular link of hub gene obtained above, we redetermined the hub-DEGs in GSE131761 according to high or low hub gene expression. Afterward, the main pathways of enrichment analysis were validated using these hub-DEGs. Finally, an experiment was conducted to validate the findings., Results: By intersecting 1415 DEGs in GSE131761, 543 DEGs in GSE9960, 5784 key modular genes, 470 ferroptosis-related genes, and 154 quercetin-related genes, we obtained one quercetin-related gene, Alox5 . Subsequently, 340 hub-DEGs were further validated according to high or low Alox5 expression. The results of the enrichment analysis revealed that hub-DEGs were mainly associated with inflammation and the immune response. Immune infiltration analysis showed that higher expression of Alox5 was related to macrophage infiltration and could be a predictor of diagnosis in patients with sepsis. The expression pattern of Alox5 was then depicted and the upregulation of Alox5 in the vital organs of septic mice was further demonstrated. In vitro and in vivo experiments showed that upregulation of Alox5 and inflammation-related cytokines induced by sepsis could be inhibited by quercetin ( p  < 0.05)., Conclusions: Alox5 may be involved in the occurrence and development of multi-organ functional disturbances in sepsis and is a reliable target of quercetin against sepsis.

Background: Emotion recognition using electroencephalogram (EEG) has become a research hotspot in the field of human-computer interaction, how to sufficiently learn complex spatial-temporal representations of emotional EEG data and obtain explainable model prediction results are still great challenges., New Method: In this study, a novel hierarchical and explainable attention network ST-SHAP which combines the Swin Transformer (ST) and SHapley Additive exPlanations (SHAP) technique is proposed for automatic emotional EEG classification. Firstly, a 3D spatial-temporal feature of emotional EEG data is generated via frequency band filtering, temporal segmentation, spatial mapping, and interpolation to fully preserve important spatial-temporal-frequency characteristics. Secondly, a hierarchical attention network is devised to sufficiently learn an abstract spatial-temporal representation of emotional EEG and perform classification. Concretely, in this decoding model, the W-MSA module is used for modeling correlations within local windows, the SW-MSA module allows for information interactions between different local windows, and the patch merging module further facilitates local-to-global multiscale modeling. Finally, the SHAP method is utilized to discover important brain regions for emotion processing and improve the explainability of the Swin Transformer model., Results: Two benchmark datasets, namely SEED and DREAMER, are used for classification performance evaluation. In the subject-dependent experiments, for SEED dataset, ST-SHAP achieves an average accuracy of 97.18%, while for DREAMER dataset, the average accuracy is 96.06% and 95.98% on arousal and valence dimension respectively. In addition, important brain regions that conform to prior knowledge of neurophysiology are discovered via a data-driven approach for both datasets., Comparison With Existing Methods: In terms of subject-dependent and subject-independent emotional EEG decoding accuracies, our method outperforms several closely related existing methods., Conclusion: These experimental results fully prove the effectiveness and superiority of our proposed algorithm., 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.)

Epstein-Barr virus (EBV) is associated with multiple types of cancers, many of which express the key viral oncoprotein Latent Membrane Protein 1 (LMP1). LMP1 is the only EBV-encoded protein whose expression is sufficient to transform both epithelial and B-cells. Although metabolism reprogramming is a cancer hallmark, much remains to be learned about how LMP1 alters lymphocyte oncometabolism. To gain insights into key B-cell metabolic pathways subverted by LMP1, we performed systematic metabolomic analyses on B cells with conditional LMP1 expression. This approach highlighted that LMP highly induces de novo purine biosynthesis, with xanthosine-5-P (XMP) as one of the most highly LMP1-upregulated metabolites. Consequently, IMPDH inhibition by mycophenolic acid (MPA) triggered apoptosis of LMP1-expressing EBV-transformed lymphoblastoid cell lines (LCL), a key model for EBV-driven immunoblastic lymphomas. Whereas MPA instead caused growth arrest of Burkitt lymphoma cells with the EBV latency I program, conditional LMP1 expression triggered their apoptosis. Although both IMPDH isozymes are expressed in LCLs, only IMPDH2 was critical for LCL survival, whereas both contributed to proliferation of Burkitt cells with the EBV latency I program. Both LMP1 C-terminal cytoplasmic tail domains critical for primary human B-cell transformation were important for XMP production, and each contributed to LMP1-driven Burkitt cell sensitivity to MPA. MPA also de-repressed EBV lytic antigens including LMP1 in latency I Burkitt cells, highlighting crosstalk between the purine biosynthesis pathway and the EBV epigenome. These results suggest novel oncometabolism-based therapeutic approaches to LMP1-driven lymphomas., Importance: Altered metabolism is a hallmark of cancer, yet much remains to be learned about how EBV rewires host cell metabolism to support multiple malignancies. While the oncogene LMP1 is the only EBV-encoded gene that is sufficient to transform murine B-cells and rodent fibroblasts, knowledge has remained incomplete about how LMP1 alters host cell oncometabolism to aberrantly drive infected B-cell growth and survival. Likewise, it has remained unknown whether LMP1 expression creates metabolic vulnerabilities that can be targeted by small molecule approaches to trigger EBV-transformed B-cell programmed cell death. We therefore used metabolomic profiling to define how LMP1 signaling remodels the B-cell metabolome. We found that LMP1 upregulated purine nucleotide biosynthesis, likely to meet increased demand. Consequently, LMP1 expression sensitized Burkitt B-cells to growth arrest upon inosine monophosphate dehydrogenase blockade. Thus, while LMP1 itself may not be a therapeutic target, its signaling induces dependence on downstream druggable host cell nucleotide metabolism enzymes, suggesting rational therapeutic approaches.

Double expression (DE) is a World Health Organization-recognized adverse prognostic factor in diffuse large B-cell lymphoma (DLBCL). However, the prognostic value of DE in the genetic subtyping era and potential mechanisms remain to be explored. We enrolled 246 DLBCL patients diagnosed between December 2021 and September 2023 in a Jiangsu Province Hospital cohort and included 930 DLBCL patients from three published studies in an external cohort. Double-expression DLBCL (DEL) in the external cohort was mainly distributed in the OTHER subtype (42.0%), EZB subtype (28.3%), and MCD subtype (15.0%), whereas the MCD subtype exhibited the highest ratio of DEL. DEL was significantly related to unfavorable overall survival (OS) and progression-free survival (PFS) in DLBCL, but only in EZB and OTHER subtypes that DEL retained remarkably adverse impacts on survivals compared to non-DEL. We explored the prognostic value of clinical and genetic parameters in DEL patients and found only ST2 showed better OS than A53 in DEL patients, whereas the other subtypes showed no significant difference. DEL showed similarities with the MCD subtype in mutation profiles. Furthermore, RNA-sequencing analyses exhibited upregulation in tumor proliferation-related pathways in DEL patients, but downregulation in extracellular matrix organization, T-cell activation and proliferation, type II interferon production, and pathways associated with cell death might contribute to the poor outcomes of DEL patients., (© 2024 The Author(s). Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.)

This study aimed to utilize blueberry pectin and calcium chloride to design a gel network structure for loading nut oils (peanut and walnut oil, respectively). The optimization of emulsion gel preparation was conducted through orthogonal experiments, utilizing the oil-holding ratio and gel strength as critical indicators. The emulsion gel was applied to the ice cream production. It was revealed that the peroxide value of the nut oil emulsion gels was significantly lower than that of nut oils. Both nut oil emulsion gel ice creams exhibited higher expansion rates, lower melting rates, and decreased hardness than the nut oil ice creams. Notably, walnut oil emulsion gel ice cream demonstrated a melting rate similar to traditional butter-based ice cream. Emulsion gel ice cream has higher fat globule instability and viscosity. Overall, the comprehensive emulsion gel ice cream indicators were comparable to conventional butter ice cream and notably superior to peanut and walnut oil ice cream. Using emulsion gel as a fat substitute in ice cream was feasible. The implications of these results were significant for advancing the utilization of nut oil emulsion gel within the ice cream industry., 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.)

Even though the power conversion efficiency (PCE) of perovskite solar cells (PSCs) is nearly approaching the Schottky-Queisser limit, low open-circuit voltage (V oc ) and severe V oc loss problems continue to impede the improvement of PCEs. Astaxanthin (ASTA) additive is introduced in the formamidinium lead triiodide (FAPbI 3 ) perovskite film as an additive, which can facilitate the transportation of charge carriers and interact with Pb 2+ by its distinctive groupings. Furthermore, the addition of ASTA decreases the defect's active energy, regulates the deep-level defect by filling up the grain boundaries (GBs), and promotes the crystallization of perovskite film. Remarkably, an enhanced quasi-Fermi level splitting (QFLS) of 1.164 eV and a reduced V oc loss of only 96 mV are realized. The champion PCE of 24.56% is attained by ASTA-modified PSCs on the basis of 22.75% PCE. Moreover, the PSCs that underwent ASTA modification demonstrate improved operational stability, ensuring consistent output in real-world scenarios. Furthermore, PSCs with an active area of 1 cm 2 are used for water electrolysis to produce hydrogen and exhibit a PCE of 22.41%. This work offers an environmentally benign solution to address the inherent issues of FAPbI 3 PSCs and lays the groundwork for the development of a prospective solar hydrogen production application., (© 2024 Wiley‐VCH GmbH.)

Influenza A virus (IAV) is a widespread pathogen that poses a significant threat to human health, causing pandemics with high mortality and pathogenicity. Given the emergence of increasingly drug-resistant strains of IAV, currently available antiviral drugs have been reported to be inadequate to meet clinical demands. Therefore, continuous exploration of safe, effective and broad-spectrum antiviral medications is urgently required. Here, we found that the small molecule compound J1 exhibited low toxicity both in vitro and in vivo. Moreover, J1 exhibits broad-spectrum antiviral activity against enveloped viruses, including IAV, respiratory syncytial virus (RSV), severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), human coronavirus OC43 (HCoV-OC43), herpes simplex virus type 1 (HSV-1) and HSV-2. In this study, we explored the inhibitory effects and mechanism of action of J1 on IAV in vivo and in vitro. The results showed that J1 inhibited infection by IAV strains, including H1N1, H7N9, H5N1 and H3N2, as well as by oseltamivir-resistant strains. Mechanistic studies have shown that J1 blocks IAV infection mainly through specific interactions with the influenza virus hemagglutinin HA2 subunit, thereby blocking membrane fusion. BALB/c mice were used to establish a model of acute lung injury (ALI) induced by IAV. Treatment with J1 increased survival rates and reduced viral titers, lung index and lung inflammatory damage in virus-infected mice. In conclusion, J1 possesses significant anti-IAV effects in vitro and in vivo, providing insights into the development of broad-spectrum antivirals against future pandemics., (© 2024. The Author(s), under exclusive licence to Shanghai Institute of Materia Medica, Chinese Academy of Sciences and Chinese Pharmacological Society.)

0D organic-inorganic metal halides (OIMHs) provide unprecedented versatility in structures and photoluminescence properties. Here, a series of bluish-white emissive 0D OIMHs, (TPE-TPP) 2 Sb 2 Br x Cl 8-x (x = 1.16 to 8), are prepared by assembling the 1-triphenylphosphonium-4-(1,2,2-triphenylethenyl)benzene cation (TPE-TPP) + with antimony halides anions. Based on experimental characterizations and theoretical calculations, the emission of the 0D OIMHs are attributed to the fluorescence of the organic cations with aggregation-induced emission (AIE) properties. The 0D structure minimized the molecular motion and intermolecular interactions between (TPE-TPP) + cations, effectively suppressing the non-radiative recombination processes. Consequently, the photoluminescence quantum efficiency (PLQE) of (TPE-TPP) 2 Sb 2 Br 1.16 Cl 6.84 is significantly enhanced to 55.4% as compared to the organic salt (TPE-TPP)Br (20.5%). The PLQE of (TPE-TPP) 2 Sb 2 Br x Cl 8-x can also be readily manipulated by halide substitution, due to the competitive processes between non-radiative recombination on the inorganic moiety and the energy transfer from inorganic to organic. In addition, electrically driven light-emitting diodes (LEDs) are fabricated based on (TPE-TPP) 2 Sb 2 Br 1.16 Cl 6.84 emitter, which exhibited bluish-white emission with a maximum external quantum efficiency (EQE) of 1.1% and luminance of 335 cd m -2 . This is the first report of electrically driven LED based on 0D OIMH with bluish-white emission., (© 2024 Wiley‐VCH GmbH.)

Digital transformation in the architecture industry encounters challenges such as data silos within design stages, between design and construction, and across the entire industry chain, including BIM and project management. This study introduces a pioneering approach for seamlessly integrating building information modeling (BIM) and product lifecycle management (PLM) within the management framework and collaborative workflows of architectural design and construction. The proposed methodology was implemented in two major projects, namely, the Wuhan Next-Generation Weather Radar Construction Project and the Hubei Center for Disease Control and Prevention Comprehensive Capacity Enhancement Project (Phase I), with the former being China's first end-to-end digitally integrated construction project. Compared with traditional projects, these implementations achieved improvements of 24.39% and 38.04%, respectively, in objective function values. The findings highlight the unique advantages of BIM-PLM integration in optimizing lifecycle management, enhancing cross-disciplinary, cross-enterprise, and cross-regional collaboration, improving project design efficiency and quality, and reducing costs and waste. This integration provides valuable insights into the digital advancement of the construction industry., (© 2024. The Author(s).)

Purpose: The survival rates of patients with stage IIB and IIC colon cancer are paradoxically inferior to that of patients with stage IIIA colon cancer. This study aimed to examine the oncological outcomes and investigate the factors that could affect the staging paradox among stage IIB, IIC, and IIIA colon cancers based on a 9-year cancer database., Methods: Patients with stage IIB (pT4aN0M0), IIC (pT4bN0M0), or IIIA (pT1-2N1M0) colon cancer were retrospectively selected from a prospectively maintained medical database from January 2011 to December 2019. Factors that might influence the staging paradox, including radicality, harvested lymph nodes, and chemotherapy administration, were examined., Results: A total of 282 patients (stage IIB, n = 59; stage IIC, n = 46; and stage IIIA, n = 177) were enrolled. Patients with stage IIB/C cancer demonstrated higher carcinoembryonic antigen levels, larger tumor size, more frequent tumor obstruction, and higher locoregional recurrence than those with stage IIIA cancer. With respect to 10-year locoregional recurrence-free survival and cancer-specific survival, patients with stage IIB and IIC cancers had significantly lower survival rates than did those with stage IIIA cancer (73.7% vs. 66.3% vs. 91.2%, P = 0.0003; 5.4% vs. 10.9% vs. 11.2%, P = 0.0023). The staging paradox persisted in patients who underwent R0 resection, had harvested lymph nodes ≥ 12, and received chemotherapy, as confirmed by multivariate regression analysis., Conclusions: Based on the inferior oncological outcomes and higher locoregional recurrence rate, this study highlighted the need for intensified cytotoxic chemotherapy specific to this recurrence pattern for patients with stage IIB/C colon cancer., (© 2024. The Author(s).)

USP25 encodes ubiquitin-specific protease 25, a key member of the deubiquitinating enzyme family that is involved in neural fate determination. Although abnormal expression in Down's syndrome was reported previously, the specific role of USP25 in human diseases has not been defined. In this study, we performed trio-based whole exome sequencing in a cohort of 319 cases (families) with generalized epilepsy of unknown aetiology. Five heterozygous USP25 variants, including two de novo and three co-segregated variants, were determined in eight individuals affected by generalized seizures and/or febrile seizures from five unrelated families. The frequency of USP25 variants showed a significantly high aggregation in this cohort compared with the East Asian population and all populations in the gnomAD database. The mean age at onset of febrile and afebrile seizures were 10 months (infancy) and 11.8 years (juvenile), respectively. The patients achieved seizure freedom, except that one had occasional nocturnal seizures at the last follow-up. Two patients exhibited intellectual disability. Usp25 was expressed ubiquitously in mouse brain with two peaks, on embryonic Days 14-16 and postnatal Day 21, respectively. In human brain, likewise, USP25 is expressed in the fetus/early childhood stage and with a second peak at ∼12-20 years old, consistent with the seizure onset age in patients during infancy and in juveniles. To investigate the functional impact of USP25 deficiency in vivo, we established Usp25 knockout mice, which showed increased seizure susceptibility compared with wild-type mice in a pentylenetetrazol-induced seizure test. To explore the impact of USP25 variants, we used multiple functional detections. In HEK293 T cells, the variant associated with a severe phenotype (p.Gln889Ter) led to a significant reduction of mRNA and protein expressions but formed stable truncated dimers with an increment of deubiquitinating enzyme activities and abnormal cellular aggregations, indicating a gain-of-function effect. The p.Gln889Ter and p.Leu1045del variants increased neuronal excitability in mouse brain, with a higher firing ability in p.Gln889Ter. These functional impairments align with the severity of the observed phenotypes, suggesting a genotype-phenotype correlation. Hence, a moderate association between USP25 and epilepsy was noted, indicating that USP25 is potentially a predisposing gene for epilepsy. Our results from Usp25 null mice and the patient-derived variants indicated that USP25 would play an epileptogenic role via loss-of-function or gain-of-function effects. The truncated variant p.Gln889Ter would have a profoundly different effect on epilepsy. Together, our results underscore the significance of USP25 heterozygous variants in epilepsy, thereby highlighting the critical role of USP25 in the brain., (© 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.)

Introduction: Rhizosphere bacterial community as a valuable indicator of soil quality and function, has been widespread studied. However, little knowledge is about the response of bacterial communities to plant-plant interaction and different fertilizers during secondary forest succession., Methods: We conducted a field pot experiment applying organic and inorganic fertilizers to monocultures and mixed cultures of dominant plant species from mid- to late-successional stages ( Salix oritrepha , Betula albosinensis , and Picea asperata ), and investigated the responses of plant growth and rhizosphere bacterial communities., Results and Discussion: Results indicated that growth rate of plant height varied among plant species, but no significant differences were observed in soil bacterial diversity and composition among plant species or inter-specific interactions under control. Compared to control, inorganic fertilizer resulted in increases in plant growth and the relative abundance of Proteobacteria , Patescibacteria , Bacteroidetes and Gemmatimonadetes , while simultaneously leading to decrease in the relative abundance of Acidobacteria , Actinobacteria , Chloroflexi , Rokubacteria and Planctomycetes . When grown with other species, the bacterial communities in the mixture resembled those of S. oritrepha in singular monoculture under inorganic fertilizer treatment, but plant growth was not affected by interspecific interaction. Unlike inorganic fertilizer, organic fertilizer significantly affected bacterial communities and increased bacterial diversity, but did not alter the effects of plant-plant interactions on bacterial communities. It was also observed that organic fertilizer facilitated later successional species' growth ( P. asperata and B. albosinensis ) by the mid-successional species ( S. oritrepha ), ultimately facilitating secondary forest succession. In addition, plants at different successional stages harbor specific bacterial communities to affect their growth, and the bacterial communities contributed more than soil properties to the variations in the plant growth of S. oritrepha and P. asperata though the bacterial communities were regulated by soil factors. This finding highlights the significance of the rhizosphere bacteria on plant growth and plant community succession. It also emphasize the importance of considering both plant-plant interactions and diverse fertilizer types in forest restoration efforts and provide valuable insights into optimizing agronomic practices for secondary forest succession., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Li, Kou, Liang, Zhao, Chen and Liu.)

Background: Hydrogen sulfide (H 2 S), the third gasotransmitter discovered, regulates a variety of physiological functions. Whether H 2 S alleviates skeletal muscle ageing by regulating autophagy has not been reported., Methods: Mice were administered 150 mg/kg/day of D-galactose (D-gal), and C2C12 myotubes were cultured in 20 g/L D-gal to induce ageing. Sodium hydrosulfide (NaHS) was employed as an exogenous donor in the treatment group. The intracellular concentration of H 2 S was quantified by the 7-azido-4-methylcoumarin fluorescence probe. The proteins involved in the ubiquitin-mediated degradation of AMPKα1 were detected by liquid chromatography tandem mass spectrometry (LC-MS/MS) and co-immunoprecipitation (Co-IP). S-sulfhydration of USP5 was tested by a biotin-switch assay. Associated proteins were analysed by western blot., Results: NaHS was found to effectively restore the H 2 S content in both ageing gastrocnemius (+91.89%, P < 0.001) and C2C12 myotubes (+27.55%, P < 0.001). In comparison to the D-gal group, NaHS was observed to increase the mean cross-sectional area of muscle fibres (+44.91%, P < 0.001), to decrease the collagen volume fraction of gastrocnemius (-81.32%, P = 0.001) and to reduce the β-galactosidase-positive area of C2C12 myotubes (-28.74%, P < 0.001). NaHS was also found to reverse the expression of muscle atrophy F box protein (MAFbx), muscle-specific RING finger protein 1 (MuRF1), Cyclin D1 and p21 in the ageing gastrocnemius tissue (MAFbx: -31.73%, P = 0.008; MuRF1: -32.37%, P = 0.003; Cyclin D1: +45.34%, P = 0.010; p21: -25.53%, P = 0.022) and C2C12 myotubes (MAFbx: -16.38%, P < 0.001; MuRF1: -16.45%, P = 0.003; Cyclin D1: +40.23%, P < 0.001; p21: -35.85%, P = 0.026). The AMPKα1-ULK1 pathway was activated and autophagy was up-regulated in NaHS-treated gastrocnemius tissue (p-AMPKα1: +61.61%, P = 0.018; AMPKα1: +30.64%, P = 0.010; p-ULK1/ULK1: +85.87%, P = 0.005; p62: -29.07%, P < 0.001; Beclin1: +24.75%, P = 0.007; light chain 3 II/I [LC3 II/I]: +55.78%, P = 0.004) and C2C12 myotubes (p-AMPKα1: +77.49%, P = 0.018; AMPKα1: +26.18%, P = 0.022; p-ULK1/ULK1: +38.34%, P = 0.012; p62: -9.02%, P = 0.014; Beclin1: +13.36%, P < 0.001; LC3 II/I: +79.38%, P = 0.017; autophagy flux: +24.88%, P = 0.034) compared with the D-gal group. The effects of NaHS on autophagy were comparable to those of acadesine and LYN-1604, and chloroquine could reverse its effects on ageing. LC-MS/MS and Co-IP experiments demonstrated that USP5 is a deubiquitinating enzyme of AMPKα1. Following the knockdown of USP5, the activation of AMPKα1 was decreased (p-AMPKα1: -42.10%, P < 0.001; AMPKα1: -43.93%, P < 0.001), autophagy was inhibited (p-ULK1/ULK1: -27.51, P = 0.001; p62: +36.00, P < 0.001; Beclin1: -22.15%, P < 0.001) and NaHS lost its ability to up-regulate autophagy. NaHS was observed to restore the expression (gastrocnemius: +62.17%, P < 0.001; C2C12 myotubes: +37.51%, P = 0.003) and S-sulfhydration (+53.07%, P = 0.009) of USP5 and reduce the ubiquitination of AMPKα1., Conclusions: H 2 S promotes the deubiquitination of AMPKα1 by increasing the expression and S-sulfhydration of USP5, thereby up-regulating autophagy and alleviating skeletal muscle ageing., (© 2024 The Author(s). Journal of Cachexia, Sarcopenia and Muscle published by Wiley Periodicals LLC.)

The occurrence of the cooked off-flavor during the thermal sterilization of green tea beverages negatively impacts their quality. This study aimed to identify the key cooked off-flavor compounds by molecular sensory science. The increase of 12 compounds, including malty (e.g., 3-methylbutanal), floral (e.g., linalool), sweet (e.g., methional), and smoky (2-methoxy-4-vinylphenol) compounds, contributed to the development of the cooked off-flavor. Additionally, the loss of five aroma compounds-dimethyl sulfide, (E)-β-ionone, 2-methylbutanal, 1-penten-3-one, and (E,Z)-2,6-nonadienal-also caused the emergence this undesirable flavor. One potential solution to reduce the cooked off-flavor was the baking of tea raw materials. While baking did not significantly reduce the concentration of off-flavor compounds, it led to an increase in eight roasty aroma compounds, such as pyrazines and pyrroles, which helped partially mask the cooked off-flavor in green tea beverages., 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.)

Massive labile carbon and nitrogen inputs into lakes change greenhouse gas emissions. However, the rapid driving mechanism from eutrophic and swampy lakes is not fully understood and is usually contradictory. Thus, we launched a short-term and anaerobic incubation experiment to explore the response of greenhouse gas emissions and microbial communities to glucose and nitrate nitrogen (NO 3 - -N) inputs. Glucose addition significantly increased CH 4 and CO 2 emissions and decreased N 2 O emissions, but there were no significant differences. NO 3 - -N addition significantly promoted N 2 O emissions but reduced CH 4 accumulative amounts, similar to the results of the Tax4Fun prediction. Bacterial relative abundance changed after glucose addition and coupled with the abundance of denitrification genes ( nirS and nirK ) decreased while maintaining a negative impact on N 2 O emissions, considerably increasing methanogenic bacteria ( mcrA1 ) while maintaining a positive impact on CH 4 emissions. Structural equation modeling showed that glucose and NO 3 - -N addition directly affected MBC content and greenhouse gas emissions. Further, MBC content was significantly negative with nirS and nirK , and positive with mcrA1 . These results significantly deepen the current understanding of the relationships between labial carbon, nitrogen, and greenhouse emissions, further highlighting that labile carbon input is the primary factor driving greenhouse gas emissions from eutrophic shallow lakes.

The asymmetric cycloaddition between N -2,2,2-trifluoroethylisatin ketimines and unsymmetrical dicarbonyl-activated alkenes catalyzed by a bifunctional squaramide has been discovered. The present study demonstrates an efficient approach for the regio-, diastereo-, and enantioselective synthesis of densely functionalized 5'-trifluoromethylated 3,2'-pyrrolidinyl spirooxindoles featuring three different types of carbonyl groups.

Currently reported circularly polarized luminescent devices are primarily based on rare earth and noble metal complexes or lead perovskite materials. Reports on electroluminescent devices employing eco-friendly luminescent materials are notably scarce. In this study, we strategically designed and synthesized manganese complexes featuring Binapo as the chiral ligand. The complex structure reveals a tetrahedral coordination configuration, with the R / S configurations exhibiting a mirror relationship. Leveraging the strong ligand field and chiral structural characteristics of Binapo, the enantiomers display red emission and exhibit significant circularly polarized luminescence with a circularly polarized luminescence asymmetric factor ( g lum ) of 5.1 × 10 -3 . The circularly polarized electroluminescent performance was investigated by using a solution processing method and host-guest doping strategy. Our efforts resulted in device performance with an external quantum efficiency (EQE) exceeding 4%, and its electroluminescent asymmetric factor ( g EL ) reached an impressive -8.5 × 10 -3 . This surpasses the performance of most devices relying on platinum (Pt) and iridium (Ir) metal complexes and perovskite related materials. Our work establishes a pathway for the development of cost-effective and environmentally friendly chiral electroluminescent materials and devices., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

The buried interface properties of the perovskite solar cells (PSCs) play a crucial role in the power conversion efficiency (PCE) and operational stability. The metal-oxide/perovskite heterogeneous interfaces are highly defective and cause serious ion migration. However, the buried and unexposed bottom interface and simultaneous stabilization of grain boundaries receive less attention and effective solutions. To tackle this problem, a solid-liquid strategy is employed by introducing oily-additive allicin at the buried interface to passivate the shallow (V I and Vo) and deep traps (V Pb and Pb I ). Interestingly, oily status allicin fills the pinholes at the heterointerface and wraps the perovskite grains, suppressing the ion migration during the photoaging process. As a result, an outstanding PCE of 25.07% is achieved with a remarkable fill factor (FF) of 84.03%. The modified devices can maintain 94.51% of the original PCE after light soaking under 1-sun illumination for 1000 h. This work demonstrates a buried interface modification method that employs an eco-friendly additive, which helps promote the development of PSCs with high performance and stability., (© 2024 Wiley‐VCH GmbH.)

Theanine (N-ethyl-γ-glutamine), as a unique non-protein amino acid, plays vital roles in abiotic stress resistance, while its roles in biotic stress resistance are still unclear. Gray mold caused by Botrytis cinerea is a major disease in strawberries. Effects of theanine on the development of gray mold, cell-wall and phenylpropanoid metabolisms in strawberries were investigated in this study. Results showed that 5 mmol L -1 theanine treatment reduced disease incidence and severity of gray mold in strawberries with antifungal activity in vitro. Meanwhile, theanine treatment enhanced the accumulation of phenolic compounds and lignin, especially ellagic acid, cyanidin, and quercetin, which was associated with increased phenylpropanoid pathway related enzyme activities. Moreover, theanine induced callose deposition and suppressed cell- wall disassembling enzymes, accompanied by higher levels of water insoluble pectin, hemicellulose and cellulose. Therefore, theanine treatment could alleviate decay of B. cinerea- inoculated strawberries by regulating phenylpropanoid and cell-wall metabolisms, maintaining higher levels of phenolic compounds and cell-wall components, thereby contributing to disease resistance and cell-wall structure integrity., Competing Interests: 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., (© 2024 The Authors.)

The effect of puffing treatment on the volatile components of green tea has been studied. A total of 155 volatile compounds were identified by using HS-SPME and SPE extraction methods, combined with gas chromatography-mass spectrometry (GC-MS). The total concentration of volatile compounds in puffed green tea increased by 2.25 times compared to that in before puffing. 12 key volatile compounds in green tea were identified before and after puffing using a combination of multivariate statistical analysis, GC-O, AEDA dilution analysis, and relative odor activity value (rOAV). The puffing process generates the Maillard reaction, where sugars react with amino acids to produce Maillard reaction products (such as pyrazine, pyrrole, furan, and their derivatives), giving them a unique baking aroma. The proportion of these compounds in the total volatile matter increased. The research results provided guidance and a theoretical basis for improving the aroma processing of green tea., Competing Interests: The authors declare no competing financial interest or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors. Published by Elsevier Ltd.)

TP53 mutation (TP53-mut) correlates with inferior survival in many cancers, whereas its prognostic role in diffuse large B-cell lymphoma (DLBCL) is still in controversy. Therefore, more precise risk stratification needs to be further explored for TP53-mut DLBCL patients. A set of 2637 DLBCL cases from multiple cohorts, was enrolled in our analysis. Among the 2637 DLBCL patients, 14.0% patients (370/2637) had TP53-mut. Since missense mutations account for the vast majority of TP53-mut DLBCL patients, and most non-missense mutations affect the function of the P53 protein, leading to worse survival rates, we distinguished patients with missense mutations. A TP53 missense mutation risk model was constructed based on a 150-combination machine learning computational framework, demonstrating excellent performance in predicting prognosis. Further analysis revealed that patients with high-risk missense mutations are significantly associated with early progression and exhibit dysregulation of multiple immune and metabolic pathways at the transcriptional level. Additionally, the high-risk group showed an absolutely suppressed immune microenvironment. To stratify the entire cohort of TP53-mut DLBCL, we combined clinical characteristics and ultimately constructed the TP53 Prognostic Index (TP53PI) model. In summary, we identified the truly high-risk TP53-mut DLBCL patients and explained this difference at the mutation and transcriptional levels., (© 2024. The Author(s).)

Chiral 3D perovskites pose challenges compared to lower-dimensional variants due to limited chiral organic cation options. Here, we present a universal and controlled method for synthesizing chiral 3D lead halide perovskites using organic amines or alcohols as chiral templates. Introducing these templates to PbCl 2 in N , N -dimethylformamide (DMF) under acidic conditions induces the crystallization of R/S [DMA]PbCl 3 (DMA = dimethylamine). The resulting structure aligns with the templates used, stemming from the helical Pb 2 Cl 9 5- chain as verified by single-crystal X-ray diffraction. Furthermore, the chiral perovskite exhibits absorption and circular dichroism (CD) signals in the high-energy band, enabling the circularly polarized light (CPL) detection in the UV spectrum. A CPL detector constructed by this chiral perovskite demonstrates excellent performance, boasting an anisotropy factor for photocurrent ( g Iph ) of 0.296. Our work not only introduces a novel and controllable method for crafting chiral perovskites but also opens new avenues for circularly polarized light detection.

Introduction: EGFR-mutated NSCLC is characterized by an immunosuppressive microenvironment that confers limited clinical effectiveness to anti-PD-1 or PD-L1 antibodies. Despite the discouraging outcomes of immunotherapy, novel immune checkpoints are constantly emerging, among which the specific vulnerability for therapeutic intervention in the context of EGFR-mutated NSCLC remains unresolved., Methods: Data sets of patient- and cell line-levels were used for screening and mutual validation of association between EGFR mutation and a panel of immune checkpoint-related genes. Regulatory mechanism was elucidated through in vitro manipulation of EGFR signaling pathway and evaluated by immunoblot analysis, quantitative polymerase chain reaction, flow cytometry, immunofluorescence staining, and chromatin immunoprecipitation. In vivo investigation of different therapeutic strategies were conducted using both immunocompetent and immunodeficient mouse models., Results: Among all screened immune checkpoints, CD47 emerged as the candidate most relevant to EGFR activation. Mechanistically, EGFR mutation constitutively activated downstream ERK and AKT pathways to respectively up-regulate the transcriptional factors c-Myc and NF-κB, both of which structurally bound to the promotor region of CD47 and actively transcribed this "don't eat me" signal. Impaired macrophage phagocytosis was observed on introduction of EGFR-sensitizing mutations in NSCLC cell line models, whereas CD47 blockade restored the phagocytic capacity and augmented tumor cell killing in both in vitro and in vivo models. Remarkably, the combination of anti-CD47 antibody with EGFR tyrosine kinase inhibitor revealed an additive antitumor activity compared with monotherapy of either antitumor agent in both immunocompetent and adaptive immunity-deficient mouse models., Conclusions: EGFR-sensitizing mutation facilitates NSCLC's escape from innate immune attack through up-regulating CD47. Combination therapy incorporating CD47 blockade holds substantial promise for clinical translation in developing more effective therapeutic approaches against EGFR-mutant NSCLC., Competing Interests: Disclosure Dr. Wu is an employee of Shenzhen Engineering Center for Translational Medicine of Precision Cancer Immunodiagnosis and Therapy, YuceBio Technology Co., Ltd. The remaining authors declare no conflict of interest, (Copyright © 2024 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.)

Single-cluster catalysts (SCCs) representing structurally well-defined metal clusters anchored on support tend to exhibit tunable catalytic performance for complex redox reactions in heterogeneous catalysis. Here we report a theoretical study on an SCC of Ru 3 @Mo 2 CO 2 MXene for N 2 -to-NH 3 thermal conversion. Our results show that Ru 3 @Mo 2 CO 2 can effectively activate N 2 and promotes its conversion to NH 3 through an association mechanism, in which the rate-determining step of NH 2 * + H* → NH 3 * has a low energy barrier of 1.29 eV. Notably, with the assistance of Mo 2 CO 2 support, the positively charged Ru 3 cluster active site can effectively adsorb and activate N 2 , leading to 0.74 |e| charge transfer from Ru 3 @Mo 2 CO 2 to the adsorbed N 2 . The supported Ru 3 also acts as an electron reservoir to regulate the charge transfer for various intermediate steps of ammonia synthesis. Microkinetic analysis shows that the turnover frequency of the N 2 -to-NH 3 conversion on Ru 3 @Mo 2 CO 2 is as high as 1.45 × 10 -2 s -1 site -1 at a selected thermodynamic condition of 48 bar and 700 K, the performance of which even surpasses that of the Ru B5 site and Fe 3 /θ-Al 2 O 3 (010) reported before. Our work provides a theoretical understanding of the high stability and catalytic mechanism of Ru 3 @Mo 2 CO 2 and guidance for further designing and fabricating MXene-based metal SCCs for ammonia synthesis under mild conditions., (© The Author(s) 2024. Published by Oxford University Press on behalf of China Science Publishing & Media Ltd.)

Studying the stoichiometric characteristics of soil nutrients aids in evaluating soil quality and deciphering the coupling of soil nutrients. The influence of migratory bird activities on the dynamics of wetland soil nutrients and their stoichiometric remains unclear. We classified the central, peripheral and adjacent natural grassy areas as severe, mild, and no bird activity (control), respectively, in Donghu Carex meadow, a representative migratory bird habitat in Poyang Lake, based on flock characteristics and initial surveys. We analyzed the contents and stoichio-metry of soil organic carbon (SOC), total nitrogen (TN), and total phosphorus (TP) across soil depths of 0-100 cm under different intensities of migratory bird activities. The results showed that the activities of migratory birds significantly impacted nutrient levels exclusively within 0-30 cm soil. Mild activities markedly enhanced SOC and TN across 0-30 cm soil, while both mild and severe activities significantly raised TP within the same depth. For the 0-100 cm soil profiles, soil C/N ratios were 10.0, 10.8, and 9.9, C/P ratios were 23.5, 30.0, and 22.7, and N/P ratios were 2.3, 2.7, and 2.3 under no, mild, and severe bird activities, respectively. Further, mild activities of migratory birds significantly increased soil C/N, C/P and N/P ratios only within the 0-30 cm depth, while the stoichiometric ratios of all soil layer had no significant difference under severe bird activity. Soil stoichiometric ratios strongly correlated with physicochemical properties. SOC, TN, and TP primarily mediated the effects of migratory bird activity on soil carbon, nitrogen, and phosphorus stoichiometric ratios in Poyang Lake wetland. In conclusion, the influence of migratory bird activity on the stoichiometric ratios of soil carbon, nitrogen, and phosphorus in Poyang Lake wetland exhibited depth threshold (approximately 30 cm), aligning with the "Intermediate Distur-bance Hypothesis". These findings could provide a new perspective for the protection of wetlands and migratory birds.

Podophyllotoxin (PPT) is a lignan derived from the roots and stems of the Podophyllum plant. However, its enterotoxicity restricts its clinical application. The underlying mechanisms by which PPT exerts its action remain largely elusive. This study aimed to evaluate the molecular mechanisms underlying PPT-induced enterotoxicity utilizing the concept of toxicological evidence chain. Changes in body weight, behavior, and histopathological and biochemical markers in rats were observed. Additionally, microbiome, metabolome, and transcriptome analyses were integrated to identify potential microorganisms, metabolic markers, and major pathways using a co-occurrence network. Our findings suggested that PPT induced pathological changes in rats, including weight loss, diarrhea, and inflammation accompanied by increased levels of IFN-γ, IL-5, IL-6, GRO/KC, and IL-12p70. The decrease in butyrate levels in the PPT group may be related to the enrichment of Firmicutes. The reduction of butyrate levels may impair the expression of PPARγ, subsequently promoting Escherichia-Shigella proliferation. Additionally, the suppression of PPARs pathway may result in the increased production of inflammatory factors, contributing to enterotoxicity. This study offers a novel understanding of the molecular mechanisms underlying PPT-induced enterotoxicity, making a significant contribution to developing strategies to mitigate PPT toxicity and prevent associated diseases., 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 Inc. All rights reserved.)

Background: Among bone diseases, osteoporosis-like skeleton, such as trabecular thinning, fracture and so on, is the main pathological change of cadmium-induced osteoporosis(Cd-OP), accompanied by brittle bone and increased fracture rate. However, the mechanism underlying cadmium-induced osteoporosis has remained elusive. Compound Lurong Jiangu Capsule (CLJC) is an experienced formula for the treatment of bone diseases, which has the effect of tonifying kidney and strengthening bones, promoting blood circulation and relieving pain., Objective: Network pharmacology and molecular docking technology combined with experiments were used to investigate the potential mechanism of CLJC in treating Cd-OP., Method: The active compounds and corresponding targets of each herb in CLJC were searched in the TCMSP and BATMAN-TCM databases. The DisGeNet, OMIM, and GeneCards databases searched for Cd-OP targets. The relationship between both of them was visualized by establishing an herb-compound-target network using Cytoscape 3.9.1 software. Gene ontology (GO), and Kyoto encyclopedia of genes and genomes (KEGG) pathway enrichment analyses were performed after determining the intersection of the targets from CLJC and Cd-OP. What's more, molecular docking was performed to validate the results. All of them were aim to obtain hud signaling pathways for further study. Finally, BAX, BCL-2, and CASPASE-3 were screened and selected for further experiments, which included bone imaging and reconstruction analysis (Micro-CT), hematoxylin-eosin Staining (HE), and western blot (WB)., Results: 106 common targets from CLJC and Cd-OP targets were identified. KEGG pathway analysis suggested that multiple signaling pathways, such as the pathways in cancer, may play roles in treatment. Verification of the molecular docking was successful. Here we showed that Cd-OP displayed Tb.Th and Tb.N significantly reduced and even broke, irregular proliferation of bone cortex, uneven and loose trabecular bone arrangement, changed in apoptosis-related proteins, such as significant upregulation of CASPASE-3, BAX protein and significant downregulation of BCL-2 protein in vivo , while CLJC rescued these phenotypes., Conclusion: This study revealed that CLJC can reduce the expression of apoptosis-related proteins, and multiple components and multiple targets inhibit Cd-OP through apoptosis signaling pathway., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Zhou, Huang, Cao, Yu, Li, Liang, Leng, Jin, Yu and Liu.)

Idiopathic pulmonary fibrosis (IPF) is the most predominant type of idiopathic interstitial pneumonia and has an increasing incidence, poor prognosis, and unclear pathogenesis. In order to investigate the molecular mechanisms underlying IPF further, we performed single-cell RNA sequencing analysis on three healthy controls and five IPF lung tissue samples. The results revealed a significant shift in epithelial cells (ECs) phenotypes in IPF, which may be attributed to the differentiation of alveolar type 2 cells to basal cells. In addition, several previously unrecognized basal cell subtypes were preliminarily identified, including extracellular matrix basal cells, which were increased in the IPF group. We identified a special population of fibroblasts that highly expressed extracellular matrix-related genes, POSTN, CTHRC1, COL3A1, COL5A2, and COL12A1. We propose that the close interaction between ECs and fibroblasts through ligand-receptor pairs may have a critical function in IPF development. Collectively, these outcomes provide innovative perspectives on the complexity and diversity of basal cells and fibroblasts in IPF and contribute to the understanding of possible mechanisms in pathological lung fibrosis., (© 2024. The Author(s).)

Objective: To summary radiating blood flow signals and evaluate their diagnostic value in differentiating benign and malignant thyroid nodules., Materials and Methods: We retrospectively recruited consecutive patients undergoing US at 4 hospitals from 2018 to 2022. In a training dataset, the correlations of US features with malignant thyroid nodules were assessed by multivariate logistic analysis. Multivariate logistic regression models involving the ACR TI-RADS score, radiating blood flow signals and their combination were built and validated internally and externally. The AUC with 95% asymptotic normal confidence interval as well as sensitivity, specificity, negative predictive value (NPV), and positive predictive value (PPV) with 95% exact binomial confidence intervals were calculated., Results: Among 2475 patients (1818 women, age: 42.47 ± 11.57; 657 men, age: 42.16 ± 11.69), there were 3187 nodules (2342 malignant nodules and 845 benign nodules). Radiating blood flow signals were an independent risk factor for diagnosing thyroid carcinoma. In the training set, the AUC of the model using the combination of radiating blood flow signals and the ACR TI-RADS score (0.95 95 % CI: [0.94, 0.97]; P < 0.001) was significantly higher than that of the ACR TI-RADS model (0.91 [0.89, 0.93]). In the two internal validation sets and the external validation set, the AUCs of the combination model were 0.97 [0.96, 0.98], 0.92 [0.88, 0.96], and 0.91 [0.86, 0.95], respectively, and were all significantly higher than that of the ACR TI-RADS score (0.92 [0.90, 0.95], 0.86 [0.81, 0.91], 0.84 [0.79, 0.89]; P < 0.001)., Conclusion: Radiating blood flow is a new US feature of thyroid carcinomas that can significantly improve the diagnostic performance vs. the ACR TI-RADS score., 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 clinical implications of CSF-ctDNA positivity in newly diagnosed diffuse large B cell lymphoma (ND-DLBCL) remains largely unexplored. One hundred ND-DLBCL patients were consecutively enrolled as training cohort and another 26 ND-DLBCL patients were prospectively enrolled in validation cohort. CSF-ctDNA positivity (CSF(+)) was identified in 25 patients (25.0%) in the training cohort and 7 patients (26.9%) in the validation cohort, extremely higher than CNS involvement rate detected by conventional methods. Patients with mutations of CARD11, JAK2, ID3, and PLCG2 were more predominant with CSF(+) while FAT4 mutations were negatively correlated with CSF(+). The downregulation of PI3K-AKT signaling, focal adhesion, actin cytoskeleton, and tight junction pathways were enriched in CSF(+) ND-DLBCL. Furthermore, pretreatment CSF(+) was significantly associated with poor outcomes. Three risk factors, including high CSF protein level, high plasma ctDNA burden, and involvement of high-risk sites were used to predict the risk of CSF(+) in ND-DLBCL. The sensitivity and specificity of pretreatment CSF-ctDNA to predict CNS relapse were 100% and 77.3%. Taken together, we firstly present the prevalence and the genomic and transcriptomic landscape for CSF-ctDNA(+) DLBCL and highlight the importance of CSF-ctDNA as a noninvasive biomarker in detecting and monitoring of CSF infiltration and predicting CNS relapse in DLBCL., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

Aims: To identify and reach consensus on dimensions and criteria of a competence assessment instrument for health professionals in relation to the process of evidence-based healthcare., Design: A two-round Delphi survey was carried out from April to June 2023., Methods: Consensus was sought from an expert panel on the instrument preliminarily established based on the JBI Model of Evidence-Based Healthcare and a rapid review of systematic reviews of relevant literature. The level of consensus was reflected by the concentration and coordination of experts' opinions and percentage of agreement. The instrument was revised significantly based on the combination of data analysis, the experts' comments and research group discussions., Results: Sixteen national and three international experts were involved in the first-round Delphi survey and 17 experts participated in the second-round survey. In both rounds, full consensus was reached on the four dimensions of the instrument, namely evidence-generation, evidence-synthesis, evidence-transfer and evidence-implementation. In round-one, the instrument was revised from 77 to 61 items. In round-two, the instrument was further revised to have 57 items under the four dimensions in the final version., Conclusion: The Delphi survey achieved consensus on the instrument. The validity and reliability of the instrument needs to be tested in future research internationally., Implications for the Profession And/or Patient Care: Systematic assessment of nurses and other health professionals' competencies in different phases of evidence-based healthcare process based on this instrument provides implications for their professional development and multidisciplinary team collaboration in evidence-based practice and better care process and outcomes., Impact: This study addresses a research gap of lacking an instrument to systematically assess interprofessional competencies in relation to the process of EBHC. The instrument covers the four phases of EBHC process with minimal criteria, highlighting essential aspects of ability to be developed. Identification of health professionals' level of competence in these aspects helps strengthen their capacity accordingly so as to promote virtuous EBHC ecosystem for the ending purpose of improving global healthcare outcomes., Reporting Method: This study was reported in line with the Conducting and REporting of DElphi studies (CREDES) guidance on Delphi studies., Patient and Public Contribution: No patient or public contribution., (© 2024 John Wiley & Sons Ltd.)

The ongoing transition within the Chinese economy assumes a pivotal role in shaping the landscape of the cultural and creative industries (CCI). Renowned for its environmentally sustainable attributes, coupled with high productivity, CCI has garnered considerable attention across diverse societal strata. This study endeavors to delineate the determinants influencing the developmental trajectory of CCI, with a focal point on City A as the primary subject of investigation, juxtaposed against Cities G, D, B, H, and X for comparative analysis, leveraging developmental data from the year 2021. Initially, the study elucidates the conceptual framework underpinning CCI and its intrinsic significance in facilitating urban metamorphosis. Subsequently, the positive impact of CCI through deep learning and information management technology is emphasized, and a cultural and creative recommendation model based on LSTM algorithm is constructed. Through performance evaluation, the recommendation accuracy for cultural and creative projects reaches 94.74 %. A robust developmental assessment model for CCI is then constructed via meticulous factor analysis of pertinent influencers. Employing factor analysis techniques, the study identifies two primary determinants exerting sway over CCI development: sustainable profitability factors and cultural influence factors. Noteworthy among the factors influencing CCI development within City A are fixed asset investment, cultural industry financing, the proliferation of university-based research institutions, and per capita cultural expenditure by residents. Of these, fixed asset investment, cultural industry financing, and the density of university research institutions prominently impinge upon sustainable profitability, with a discernible impact weight of 0.738 in the evaluative framework of CCI development, thus significantly shaping its trajectory. Moreover, consumer psychological factors, particularly market consumption patterns, are observed to exert a discernible influence on CCI evolution. This study augurs fresh insights into the realm of CCI development, infusing it with renewed vigor and vitality. Moreover, it underscores the inherent interdependence and positive correlation among the various research factors, offering novel perspectives and methodologies germane to the advancement of urban CCI., Competing Interests: 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., (© 2024 The Authors.)

Diffuse large B-cell lymphoma (DLBCL), accounts for 30-40% of newly diagnosed lymphomas, has an overall cure rate of approximately 60%. Despite previous reports suggesting a negative prognostic association between CCND3 mutations and Burkitt lymphoma, their prognostic implications in DLBCL remain controversial. To investigate this, we evaluated CCND3 mutation status in 2059 DLBCL patient samples from four database (integrated cohort) and additional 167 DLBCL patient samples in our center (JSPH cohort). The mutation was identified in 5.5% (113/2059) of the cases in the integrated cohort, with 86% (97/113) found in exon 5. Furthermore, P284, R271, I290 and Q276 are described as CCND3 mutation hotspots. CCND3 mutation was associated with decreased overall survival (OS) in the integrated cohort (P = 0.0407). Further subgroup analysis revealed that patients diagnosed as EZB subtype DLBCL by LymphGen algorithm with CCND3 mutations had poorer OS than patients diagnosed as EZB subtype without CCND3 mutations (P = 0.0140). Using the next-generation sequencing (NGS) in the JSPH cohort, it was found that both cell cycle and DNA replication pathways were highly upregulated in patients with CCND3 mutations. Our results suggest that CCND3 mutations can serve as a novel prognostic factor in DLBCL pathogenesis. Consequently, the development of personalized therapeutic strategies for DLBCL patients with CCND3 mutations might enhance their prognosis., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Mantle cell lymphoma (MCL) is an incurable and aggressive subtype of non-Hodgkin B-cell lymphoma. Increased lipid uptake, storage, and lipogenesis occur in a variety of cancers and contribute to rapid tumor growth. However, no data has been explored for the roles of lipid metabolism reprogramming in MCL. Here, we identified aberrant lipid metabolism reprogramming and PRMT5 as a key regulator of cholesterol and fatty acid metabolism reprogramming in MCL patients. High PRMT5 expression predicts adverse outcome prognosis in 105 patients with MCL and GEO database (GSE93291). PRMT5 deficiency resulted in proliferation defects and cell death by CRISPR/Cas9 editing. Moreover, PRMT5 inhibitors including SH3765 and EPZ015666 worked through blocking SREBP1/2 and FASN expression in MCL. Furthermore, PRMT5 was significantly associated with MYC expression in 105 MCL samples and the GEO database (GSE93291). CRISPR MYC knockout indicated PRMT5 can promote MCL outgrowth by inducing SREBP1/2 and FASN expression through the MYC pathway., 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.)

In this study, Co/Ni-NC catalyst with hetero-diatomic Co/Ni active sites dispersed on nitrogen-doped carbon matrix is synthesized via the controlled pyrolysis of ZIF-8 containing Co 2+ and Ni 2+ compounds. Experimental characterizations and theoretical calculations reveal that Co and Ni are atomically and uniformly dispersed in pairs of CoN 4 -NiN 4 with an intersite distance ≈0.41 nm, and there is long-range d-d coupling between Co and Ni with more electron delocalization for higher bifunctional activity. Besides, the in situ grown carbon nanotubes at the edges of the catalyst particles allow high electronic conductivity for electrocatalysis process. Electrochemical evaluations demonstrate the superior ORR and OER bifunctionality of Co/Ni-NC catalyst with a narrow potential gap of only 0.691 V and long-term durability, significantly prevailing over the single-atom Co-NC and Ni-NC catalysts and the benchmark Pt/C and RuO 2 catalysts. Co/Ni-NC catalyzed Zn-air batteries achieve a high specific capacity of 771 mAh g -1 and a long continuous operation period up to 340 h with a small voltage gap of ≈0.65 V, also much superior to Pt/C-RuO 2 ., (© 2024 The Authors. Advanced Science published by Wiley‐VCH GmbH.)

B-lymphocytes play major adaptive immune roles, producing antibody and driving T-cell responses. However, how immunometabolism networks support B-cell activation and differentiation in response to distinct receptor stimuli remains incompletely understood. To gain insights, we systematically investigated acute primary human B-cell transcriptional, translational and metabolomic responses to B-cell receptor (BCR), Toll-like receptor 9 (TLR9), CD40-ligand (CD40L), interleukin-4 (IL4) or combinations thereof. T-independent BCR/TLR9 co-stimulation, which drives malignant and autoimmune B-cell states, jointly induced PD-L1 plasma membrane expression, supported by NAD metabolism and oxidative phosphorylation. BCR/TLR9 also highly induced the transaminase BCAT1, which localized to lysosomal membranes to support branched chain amino acid synthesis and mTORC1 hyperactivation. BCAT1 inhibition blunted BCR/TLR9, but not CD40L/IL4-triggered B-cell proliferation, IL10 expression and BCR/TLR pathway-driven lymphoma xenograft outgrowth. These results provide a valuable resource, reveal receptor-mediated immunometabolism remodeling to support key B-cell phenotypes including PD-L1 checkpoint signaling, and identify BCAT1 as a novel B-cell therapeutic target., Competing Interests: A.E.P. is an employee of Ergon Pharmaceuticals Ltd. V.K.M. is a consultant to 5AM Ventures. A.M.M. has research funding from Janssen, Epizyme and Daiichi Sankyo. A.M.M. has consulted for Exo Therapeutics, Treeline Biosciences, Astra Zeneca, Epizyme. M.R.G reports research funding from Sanofi, Kite/Gilead, Abbvie and Allogene; consulting for Abbvie, Allogene and Bristol Myers Squibb; honoraria from BMS, Daiichi Sankyo and DAVA Oncology; and stock ownership of KDAc Therapeutics. All other authors declare no competing interests.

Corticosterone (CORT) damages hippocampal neurons as well as induces neuroinflammation. The tricarboxylic acid cycle metabolite itaconate has an anti-inflammatory role. Necroptosis is a form of programmed cell death, also known as inflammatory cell death. Menin is a multifunctional scaffold protein, which deficiency aggravates neuroinflammation. In this study, we explored whether itaconate inhibits CORT-induced neuroinflammation as well as necroptosis and further investigated the mediatory role of Menin in this protective effect of itaconate by using an exposure of CORT to HT22 cells (a hippocampal neuronal cell line). The viability of HT22 cells was examined by the cell counting kit 8 (CCK-8). The morphology of HT22 cells was observed by transmission electron microscope (TEM). The expressions of necroptosis-related proteins (p-RIP1/RIP1, p-RIP3/RIP3, and p-MLKL/MLKL) were evaluated by western blotting. The contents of inflammatory factors were detected by an enzyme-linked immunosorbent assay (ELISA) kit. Our results showed that CORT increases the contents of pro-inflammatory factors (IL-1β, TNF-α) as well as decreases the contents of anti-inflammatory factors (IL-4, IL-10) in HT22 cells. We also found that CORT increases the expressions of necroptosis-related proteins (p-RIP1/RIP1, p-RIP3/RIP3, and p-MLKL/MLKL) and decreases the cell viability in HT22 cells, indicating that CORT induces necroptosis in HT22 cells. Itaconate improves CORT-induced neuroinflammation and necroptosis. Furthermore, itaconate upregulates the expression of Menin in CORT-exposed HT22 cells. Importantly, silencing Menin abolishes the antagonistic effect of itaconate on CORT-induced necroptosis and neuroinflammation. In brief, these results indicated that itaconate protects HT22 cells against CORT-induced neuroinflammation and necroptosis via upregulating Menin., (© 2024. The Author(s) under exclusive licence to University of Navarra.)

Root architecture and function are critical for plants to secure water and nutrient supply from the soil, but environmental stresses alter root development. The phytohormone jasmonic acid (JA) regulates plant growth and responses to wounding and other stresses, but its role in root development for adaptation to environmental challenges had not been well investigated. We discovered a novel JA Upregulated Protein 1 gene (JAUP1) that has recently evolved in rice and is specific to modern rice accessions. JAUP1 regulates a self-perpetuating feed-forward loop to activate the expression of genes involved in JA biosynthesis and signalling that confers tolerance to abiotic stresses and regulates auxin-dependent root development. Ectopic expression of JAUP1 alleviates abscisic acid- and salt-mediated suppression of lateral root (LR) growth. JAUP1 is primarily expressed in the root cap and epidermal cells (EPCs) that protect the meristematic stem cells and emerging LRs. Wound-activated JA/JAUP1 signalling promotes crosstalk between the root cap of LR and parental root EPCs, as well as induces cell wall remodelling in EPCs overlaying the emerging LR, thereby facilitating LR emergence even under ABA-suppressive conditions. Elevated expression of JAUP1 in transgenic rice or natural rice accessions enhances abiotic stress tolerance and reduces grain yield loss under a limited water supply. We reveal a hitherto unappreciated role for wound-induced JA in LR development under abiotic stress and suggest that JAUP1 can be used in biotechnology and as a molecular marker for breeding rice adapted to extreme environmental challenges and for the conservation of water resources., (© 2024 The Authors. Plant Biotechnology Journal published by Society for Experimental Biology and The Association of Applied Biologists and John Wiley & Sons Ltd.)

Diffuse large B-cell lymphoma (DLBCL) is a severe non-Hodgkin's lymphoma. Life expectancy has improved with rituximab, but cause-specific mortality data is lacking. Using the Surveillance, Epidemiology, and End Results (SEER) database to study 27,449 individuals aged 20-74 years diagnosed with primary DLBCL who received chemotherapy between 2000 and 2019, we calculated standardized mortality rate (SMR) and excess absolute risk (EAR) and examined the connection between age, sex, time after diagnosis, and cause of death. Based on 12,205 deaths, 68.7% were due to lymphoma, 20.1% non-cancer causes, and 11.2% other cancers. Non-cancer mortality rates (SMR 1.2; EAR, 21.5) increased with DLBCL compared to the general population. The leading non-cancer death causes were cardiovascular (EAR, 22.6; SMR, 1.6) and infectious (EAR, 9.0; SMR, 2.9) diseases with DLBCL. Risks for non-cancer death and solid neoplasms are highest within the first diagnosis year, then decrease. Among socioeconomic factors, being white, being married, and having a higher income were favorable factors for reducing non-cancer mortality. To improve survival, close surveillance, assessment of risk factors, and early intervention are needed., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Auricularia cornea var. Li., as an edible mushroom rich in various nutrients, could be widely used in noodle food. This study aimed to investigate the effect of Auricularia cornea var. Li. (AU) powder on the gel properties, structure and quality of starch noodles. Taking the sample without adding AU powder as a control, the addition of AU powder enhanced the peak viscosity, trough viscosity, final viscosity, breakdown, setback, peak time, gelatinization temperature, G' (storage modulus) and G'' (loss modulus). Meanwhile, the incorporation of AU powder significantly enhanced the stability of the starch gel structure and contributed to a more ordered microstructure also promoting the short-term aging of starch paste. In vitro digestion results displayed lower rapid digestibility (21.68%) but higher resistant starch content (26.58%) with the addition of AU powder and increased breaking rate, cooking loss, swelling index and a* and b* values. However, it decreased dry matter content and L*, particularly the reducing sugar content significantly increased to 4.01% ( p < 0.05), and the total amino acid content rose to 349.91 mg/g. The GC-IMS library identified 51 VOCs, and the OPLS-DA model classified 18 VOCs (VIP > 1). Overall, the findings indicate that starch noodles with the addition of AU powder may provide greater nutritional quality, gel stability and starch antidigestibility., Competing Interests: The authors declare no conflicts of interest.

Background: The territory of D3-D4 lymphadenectomy for upper rectal and sigmoid colon cancer varies, and its oncological efficacy is unclear. This prospective study aimed to standardize the surgical technique of robotic D3-D4 lymphadenectomy and clarify its oncologic significance., Methods: Patients with upper rectal or sigmoid colon cancer with clinically suspected more than N2 lymph node metastasis were prospectively recruited to undergo standardized robotic D3-D4 lymphadenectomy. Immediately postsurgery, the retrieved lymph nodes were mapped to five N3-N4 nodal stations: the inferior mesenteric artery, para-aorta, inferior vena cava, infra-renal vein, and common iliac vessels. Patients were stratified according to their nodal metastasis status to compare their clinicopathological data and overall survival. Univariate and multivariate analyses were performed to determine the relative prognostic significance of the five specific nodal stations. Surgical outcomes and functional recovery of the patients were assessed using the appropriate variables., Results: A total of 104 patients who successfully completed the treatment protocol were assessed. The standardized D3-D4 lymph node dissection harvested sufficient lymph nodes (34.4±7.2) for a precise pathologic staging. Based on histopathological analysis, 28 patients were included in the N3-N4 nodal metastasis-negative group and 33, 34, and nine patients in the single-station, double-station, and triple-station nodal metastasis-positive groups, respectively. Survival analysis indicated no significant difference between the single-station nodal metastasis-positive and N3-N4 nodal metastasis-negative groups in the estimated 5-year survival rate [53.6% (95% CI: 0.3353-0.7000) vs. 71.18% (95% CI: 0.4863-0.8518), P=0.563], whereas patients with double-station or triple-station nodal metastatic disease had poor 5-year survival rates (24.76 and 22.22%), which were comparable to those of AJCC/UICC stage IV disease than those with single-station metastasis-positive disease. Univariate analysis showed that the metastatic status of the five nodal stations was comparable in predicting the overall survival; in contrast, multivariate analysis indicated that common iliac vessels and infra-renal vein were the only two statistically significant predictors (P<0.05) for overall survival., Conclusions: Using a robotic approach, D3-D4 lymph node dissection could be safely performed in a standardized manner to remove the relevant N3-N4 lymphatic basin en bloc, thereby providing significant survival benefits and precise pathological staging for patients. This study encourages further international prospective clinical trials to provide more solid evidence that would facilitate the optimization of surgery and revision of the current treatment guidelines for such a clinical conundrum., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)