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Background: Ubiquitination, a major post-translational modification, significantly impacts tumorigenesis, progression, and prognosis. This study aims to classify colon cancer at the molecular level and create a reliable signature using ubiquitination-related genes (URGs) to assess the immune microenvironment and prognosis. Methods: We employed non-negative matrix factorization to subtype colon cancer based on ubiquitination-related gene (URG) expression patterns. Quantitative scores for 28 immune cell infiltrates and the tumor microenvironment were computed using single-sample gene set enrichment analysis (ssGSEA) and the Estimate algorithm. Subtype feature genes were selected through Lasso logistic regression and SVM-RFE algorithm. The ubiquitination-related signature was constructed using univariate Cox, Lasso, and stepwise regression methods to categorize patients into high and low-risk groups. Validation included log-rank tests, receiver operating characteristic (ROC) analysis, decision curve analysis (DCA), and external dataset validation. Immune therapy response was compared using Tumor Immune Dysfunction and Exclusion (TIDE), Immunophenoscore (IPS), and submap analyses. Clinical variables and risk scores were integrated into an enhanced nomogram. The early diagnostic value of four URGs was confirmed via quantitative real-time polymerase chain reaction (qRT-PCR) and immunohistochemistry. The cell proliferation was assessed through colony formation, EdU staining, and xenograft tumorigenesis assays. Results: Prognostic ubiquitination-related genes (URGs) stratified patients into subtypes, revealing differences in survival, immune cell infiltration, and pathological staging. A signature of 6 URGs (ARHGAP4, MID2, SIAH2, TRIM45, UBE2D2, WDR72) was identified from 57 subtype-related genes. The high-risk group exhibited characteristics indicative of enhanced epithelial-mesenchymal transition, immune escape, immunosuppressive myeloid-derived suppressor cells, regulatory T cell infiltration, and lower immunogenicity. In contrast, the low-risk group demonstrated the opposite trend but showed a better response to CTLA4 checkpoint inhibitors. The predictive performance of the nomogram significantly improved with the integration of risk score, stage, and age. ARHGAP4 and SIAH2 exhibit promising early diagnostic capabilities. Additionally, WDR72 knockdown significantly inhibited CRC cell proliferation both in vitro and in vivo. Conclusion: Our developed ubiquitination-related signature and genes serve as promising biomarkers for colon cancer prognosis, immune microenvironment, and diagnosis.

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A 38-year-old man came to our outpatient department with abdominal pain. The computed tomography (CT) scan shows no obvious abnormalities. The colonoscopy showed a submucosal eminence about 0.6cm in diameter in ascending colon, with a yellow surface color and moderate motion. Subsequently, we performed endoscopic mucosal dissection (ESD) surgery on the patient. The postoperative pathology revealed a submucosal granular cell tumor (GCT) of the ascending colon with a diameter of about 4mm. The immunohistochemistry suggestsed CD117 (-), Desmin (mucosal muscle +), S-100 (+++), CD68 (++), SOX-10 (++), Syn (+), CgA (-) , and Ki-67 (approximately 5%+).

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OBJECTIVE: To investigate the effect of pre-treatment plasma Epstein-Barr virus (EBV) DNA copy number on the clinical features and prognosis of patients with adult secondary hemophagocytic lymphohistiocytosis(sHLH). METHODS: The clinical characteristics, survival rate, and prognostic factors of 171 patients with adult sHLH treated at Jiangsu Province Hospital from June 2017 to January 2022 were retrospectively analyzed in this study. Patients were divided into three groups, including the EBV DNA-negative group(<5.0×102 copies/ml), lower EBV-DNA loads group(5.0×102-8.51×104 copies/ml), and higher EBV-DNA loads group(＞8.51×104 copies/ml), according to pre-treatment plasma EBV-DNA copy number. Cox regression model was established for screening prognostic factors. Adult sHLH survival prediction model was constructed and realized through the nomogram based on EBV-DNA load after adjusted the factors affecting survival of etiology and treatment strategy.Concordance index (C-index) and calibration curves were calculated to verify model predictive and discriminatory capacity. RESULTS: Among 171 adult sHLH patients, 84 patients were not infected with EBV (EBV DNA-negative group), and 87 with EBV (EBV DNA-positive group, 48 lower EBV-DNA loads group and 39 higher EBV-DNA loads group). Consistent elevations in the levels of liver enzymes (ALT and AST), LDH, TG, ß 2-microglobulin and ferritin across the increasing of EBV-DNA load (all P <0.05), while the levels of fibrinogen decrease (P <0.001). The median follow-up time was 52 days (range 20-230 days), and 123 patients died. The overall survival (OS) rate of patients in EBV DNA-positive group was lower than that in EBV DNA-negative group (median OS: 40 days vs 118 days, P <0.001). Higher EBV-DNA loads had worse OS (median OS: 24 days vs 45 days vs 118 days, P <0.0001 for trend) compared to lower EBV-DNA loads and EBV DNA-negative group. Multivariate Cox analysis revealed that higher EBV-DNA loads (P =0.005), fibrinogen≤1.5 g/L (P ＝0.012), ferritin (P ＝0.041), associated lymphoma (P ＝0.002), and anti-tumor based strategy (P ＝0.001) were independent prognostic factors for OS. The C-indexes of 30 day, 90 days, 365 days survival rate were all greater than 0.8 of the nomogram model and calibration curves provided credibility to their predictive capability. Subgroup analysis showed that patients with higher EBV-DNA loads had a significantly worse prognosis in adult sHLH who were women, ferritin＞5 000 µg/L, ß2-microglobulin＞7.4 mmol/L and regardless of age, etiologies, HScore points. CONCLUSION: The EBV-DNA load is a strong and independent predictor for survival in patients with sHLH. The prognostic nomogram based on EBV-DNA loads was dependable and provides a visual tool for evaluating the survival of adult sHLH.

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Photo-assisted Zn-air batteries can accelerate the kinetics of oxygen reduction and oxygen evolution reactions (ORR/OER); however, challenges such as rapid charge carrier recombination and continuous electrolyte evaporation remain. Herein, for the first time, piezoelectric catalysis is introduced in a photo-assisted Zn-air battery to improve carrier separation capability and accelerate the ORR/OER kinetics of the photoelectric cathode. The designed microhelical catalyst exploits simple harmonic vibrations to regenerate the built-in electric field continuously. Specifically, in the presence of the low-frequency kinetic energy that occurs during water flow, the piezoelectric-photocoupling catalyst of poly(vinylidene fluoride-co-trifluoroethylene)@ferric oxide(Fe@P(V-T)) is periodically deformed, generating a constant reconfiguration of the built-in electric field that separates photogenerated electrons and holes continuously. Further, on exposure to microvibrations, the gap between the charge and discharge potentials of the Fe@P(V-T)-based photo-assisted Zn-air battery is reduced by 1.7 times compared to that without piezoelectric assistance, indicating that piezoelectric catalysis is highly effective for enhancing photocatalytic efficiency. This study provides a thorough understanding of coupling piezoelectric polarization and photo-assisted strategy in the field of energy storage and opens a fresh perspective for the investigation of multi-field coupling-assisted Zn-air batteries.

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BACKGROUND: Heart failure (HF), which is caused by cardiac overload and injury, is linked to significant mortality. Writers of RNA modification (WRMs) play a crucial role in the regulation of epigenetic processes involved in immune response and cardiovascular disease. However, the potential roles of these writers in the immunological milieu of HF remain unknown. METHODS: We comprehensively characterized the expressions of 28 WRMs using datasets GSE145154 and GSE141910 to map the cardiac immunological microenvironment in HF patients. Based on the expression of WRMs, the immunological cells in the datasets were scored. RESULTS: Single-cell transcriptomics analysis (GSE145154) revealed immunological dysregulation in HF as well as differential expression of WRMs in immunological cells from HF and non-HF (NHF) samples. WRM-scored immunological cells were positively correlated with the immunological response, and the high WRM score group exhibited elevated immunological cell infiltration. WRMs are involved in the differentiation of T cells and myeloid cells. WRM scores of T cell and myeloid cell subtypes were significantly reduced in the HF group compared to the NHF group. We identified a myogenesis-related resident macrophage population in the heart, Macro-MYL2, that was characterized by an increased expression of cardiomyocyte structural genes (MYL2, TNNI3, TNNC1, TCAP, and TNNT2) and was regulated by TRMT10C. Based on the WRM expression pattern, the transcriptomics data (GSE141910) identified two distinct clusters of HF samples, each with distinct functional enrichments and immunological characteristics. CONCLUSION: Our study demonstrated a significant relationship between the WRMs and immunological microenvironment in HF, as well as a novel resident macrophage population, Macro-MYL2, characterized by myogenesis. These results provide a novel perspective on the underlying mechanisms and therapeutic targets for HF. Further experiments are required to validate the regulation of WRMs and Macro-MYL2 macrophage subtype in the cardiac immunological milieu.

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Vibrio vulnificus (Vv) is known to cause life-threatening infections, particularly septicemia. These patients often exhibit elevated levels of pro-inflammatory cytokines. While it is established that mitogen-activated protein kinase (MAPK)-interacting kinase (MNK) contributes to the production of pro-inflammatory cytokines, the role of MNK in macrophages during Vv infection remains unclear. In this study, we investigate the impact of MNK on macrophages. We demonstrate that the inhibition of MNK in J774A.1 cells, when treated with lipopolysaccharide or Vv, resulted in decreased production of tumor necrosis factor alpha and interleukin-6, without affecting their transcription. Interestingly, treatment with MNK inhibitor CGP57380 led to enhanced phosphorylation of MNK1 but decreased phosphorylation of eIF4E. Moreover, MNK1 knockout cells exhibited an increased capacity for phagocytosis and clearance of Vv, with more acidic phagosomes than the parental cells. Notably, CGP57380 did not impact phagocytosis, bacterial clearance, or phagosome acidification in Vv-infected J774A.1 cells. Considering the reported association between MNK and mammalian target of rapamycin complex 1 (mTORC1) activation, we investigated the mTORC1 signaling in MNK1 knockout cells infected with Vv. Our results revealed that attenuation of the mTORC1 signaling in these cells and treatment with the mTORC1 inhibitor rapamycin significantly enhanced bacterial clearance in J774A.1 cells following Vv infection. In summary, our findings suggest that MNK promotes the Vv-induced cytokine production in J774A.1 cells without affecting their transcription levels. MNK1 appears to impair the phagocytosis, bacterial clearance, and phagosome acidification in Vv-infected J774A.1 cells through the MNK1-mTORC1 signaling pathway rather than the MNK1-eIF4E signaling pathway. Our findings highlight the importance of the MNK1-mTORC1 pathway in modulating macrophage responses to Vv infection. IMPORTANCE: Mitogen-activated protein kinase (MAPK)-interacting kinase (MNK) plays a role in promoting the production of tumor necrosis factor alpha and interleukin-6 in macrophages during Vibrio vulnificus (Vv) infection. Inhibition or knockout of MNK1 in J774A.1 cells resulted in reduced cytokine production without affecting their transcription levels. MNK1 also impairs phagocytosis, bacterial clearance, and phagosome acidification in Vv-infected cells through the MNK1-mammalian target of rapamycin complex 1 (mTORC1) signaling pathway. The findings highlight the importance of the MNK1-mTORC1 pathway in modulating macrophage responses to Vv infection.

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Uncontrollable interfacial side reactions generated from common aqueous electrolytes, just like the hydrogen evolution reaction (HER) and dendrite growth, have severely prevented the practical application of zinc-ion batteries (ZIBs). Solid-state ZIBs are considered to be an efficient strategy by adopting high-quality solid-state electrolytes (SSEs). Here, by confining deep eutectic electrolyte (DEE) into the nanochannels of metal-organic framework (MOF)-PCN-222, a stable DEE@PCN-222 SSE with internal Zn2+ transport channels was obtained. A distinctive ion-transport network composed of DEE and PCN-222 in the interior of DEE@PCN-222 realizes the efficient Zn2+ conduction, contributing to high ionic conductivity of 3.13×10-4 S cm-1 at room temperature, low activation energy of 0.12 eV, and a high Zn2+ transference number of 0.74. Furthermore, experimental and theoretical investigations demonstrate that DEE@PCN-222 with its unique channel structure could homogeneously regulate the Zn2+ distribution and effectively alleviate the side reactions. Highly reversible Zn plating/stripping performance of 2476 h can be realized by the SSE. The solid-state ZIBs show a specific capacity of 306 mAh g-1 and display cycling stability of 517 cycles. This unique design concept provides a new perspective in realizing the high-safety and high-performance ZIBs.

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Chemically self-recharging zinc ion batteries (ZIBs), which are capable of auto-recharging in ambient air, are promising in self-powered battery systems. Nevertheless, the exclusive reliance on chemical energy from oxygen for ZIBs charging often would bring some obstacles in charging efficiency. Herein, we develop photo-assisted chemically self-recharging aqueous ZIBs with a heterojunction of MoS2/SnO2 cathode, which are favorable to enhancing both the charging and discharging efficiency as well as the chemical self-charging capabilities under illumination. The photo-assisted process promotes the electron transfer from MoS2/SnO2 to oxygen, accelerating the occurrence of the oxidation reaction during chemical self-charging. Furthermore, the electrons within the MoS2/SnO2 cathode exhibit a low transfer impedance under illumination, which is beneficial to reducing the migration barrier of Zn2+ within the cathode and thereby facilitating the uniform inserting of Zn2+ into MoS2/SnO2 cathode during discharging. This photo-assisted chemical self-recharging mechanism enables ZIBs to attain a maximum self-charging potential of 0.95 V within 3 hours, a considerable self-charging capacity of 202.5 mAh g-1 and excellent cycling performance in a self-charging mode. This work not only provides a route for optimizing chemical self-charging energy storage, but also broadens the potential application of aqueous ZIBs.

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The lack of stable solid-state electrolytes (SSEs) with high-ionic conductivity and rational design of electrode/electrolyte interfaces remains challenging for solid-state lithium batteries. Here, for the first time, a high-performance solid-state lithium-oxygen battery is developed based on the Li-ion-conducted hydrogen-bonded organic framework (LHOF) electrolyte and the core-shell HOF-DAT@CNT cathode with a few layers of HOF-DAT on surface of carbon nanotubes. Benefiting from the abundant dynamic hydrogen bonding network in LHOF-DAT SSEs, fast Li+ ion transport (2.2 × 10-4 S cm-1), a high Li+ transfer number (0.88), and a wide electrochemical window of 5.05 V are achieved. Symmetric batteries constructed with LHOF-DAT SSEs exhibit a stably cycled duration of over 1400 h, which mainly stems from the jumping sites that promote a uniformly high rate of Li+ flux and the hydrogen-bonding network structure that can relieve the structural changes during Li+ transport. LHOF-DAT SSEs-based Li-O2 batteries exhibit high specific capacity (10335 mAh g-1), and stable cycling life up to 150 cycles. Moreover, the solid-state lithium metal battery with LHOF-DAT SSEs endow good rate capability (128.8 mAh g-1 at 1 C), long-term discharge/charge stability (210 cycles). The design of LHOF-DAT SSEs opens an avenue for the development of novel SSEs-based solid-state lithium batteries.

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Underwater acoustic target recognition has emerged as a prominent research area within the field of underwater acoustics. However, the current availability of authentic underwater acoustic signal recordings remains limited, which hinders data-driven acoustic recognition models from learning robust patterns of targets from a limited set of intricate underwater signals, thereby compromising their stability in practical applications. To overcome these limitations, this study proposes a recognition framework called M3 (multitask, multi-gate, multi-expert) to enhance the model's ability to capture robust patterns by making it aware of the inherent properties of targets. In this framework, an auxiliary task that focuses on target properties, such as estimating target size, is designed. The auxiliary task then shares parameters with the recognition task to realize multitask learning. This paradigm allows the model to concentrate on shared information across tasks and identify robust patterns of targets in a regularized manner, thus, enhancing the model's generalization ability. Moreover, M3 incorporates multi-expert and multi-gate mechanisms, allowing for the allocation of distinct parameter spaces to various underwater signals. This enables the model to process intricate signal patterns in a fine-grained and differentiated manner. To evaluate the effectiveness of M3, extensive experiments were implemented on the ShipsEar underwater ship-radiated noise dataset. The results substantiate that M3 has the ability to outperform the most advanced single-task recognition models, thereby achieving the state-of-the-art performance.

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Underwater acoustic target recognition based on passive sonar faces numerous challenges in practical maritime applications. One of the main challenges lies in the susceptibility of signal characteristics to diverse environmental conditions and data acquisition configurations, which can lead to instability in recognition systems. While significant efforts have been dedicated to addressing these influential factors in other domains of underwater acoustics, they are often neglected in the field of underwater acoustic target recognition. To overcome this limitation, this study designs auxiliary tasks that model influential factors (e.g., source range, water column depth, or wind speed) based on available annotations and adopts a multi-task framework to connect these factors to the recognition task. Furthermore, we integrate an adversarial learning mechanism into the multi-task framework to prompt the model to extract representations that are robust against influential factors. Through extensive experiments and analyses on the ShipsEar dataset, our proposed adversarial multi-task model demonstrates its capacity to effectively model the influential factors and achieve state-of-the-art performance on the 12-class recognition task.

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OBJECTIVES: To assess the efficacy, safety, and impact on serum cytokines of olopatadine hydrochloride (OLP) combined with desloratadine citrate disodium (DES) in treating urticaria. METHODS: We retrospectively analyzed 114 urticaria patients treated at the Affiliated Hospital of Xinyang Vocational and Technical College from March 2020 to March 2023. The control group (55 patients) received DES, while the research group (59 patients) received OLP+DES combination therapy. We compared efficacy, safety (including epigastric pain, dry mouth, lethargy, dizziness, and fatigue), changes in serum cytokines (interleukin [IL]-2, IL-4, and interferon [IFN]-γ), symptom resolution (wheal number, wheal size, and itching degree), and 3-month recurrence rates. A univariate analysis was also conducted to identify factors influencing urticaria recurrence. RESULTS: The research group exhibited a significantly higher overall efficacy rate, lower incidence of adverse events, and reduced recurrence rates at 3 months (all P<0.05) compared to the control group. Post-treatment, the research group showed significant increases in IL-2 and IFN-γ levels and reductions in IL-4 levels, wheal number, wheal size, and itching degree (all P<0.05). Factors such as history of drinking/smoking, IL-2 levels, and treatment method were associated with urticaria recurrence (all P<0.05). CONCLUSIONS: The combination of OLP and DES is an effective and safe treatment option for urticaria, significantly improving serum cytokine profiles, alleviating symptoms, and reducing recurrence risk.

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This study explores the manipulation of photonic nanojets (PNJs) via axial illumination of cylindrical dielectric particles with cylindrical vector beams (CVBs). The edge diffraction effect of cylindrical particles is harnessed to achieve the near-field focusing of CVBs, minimizing the spherical aberration's impact on the quality of the PNJ. By discussing how beam width, refractive index, and particle length affect PNJs under radially polarized incidence, a simple and effective approach is demonstrated to generate rod-like PNJs with uniform transmission distances and super-diffraction-limited PNJs with pure longitudinal polarization. Azimuthal polarization, on the other hand, generates tube-like PNJs. These PNJs maintain their performance across scale. Combining edge diffraction with CVBs offers innovative PNJ modulation schemes, paving the way for potential applications in particle trapping, super-resolution imaging, photo-lithography, and advancing mesotronics and related fields.

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Two previously uncharacterized compounds, an aconitine-type C19-diterpenoid alkaloid (1) and a napelline-type diterpenoid alkaloid C20-diterpenoid alkaloid (2), as well as ten known compounds (3-12), were isolated from Aconitum pendulum. Their structures were elucidated based on spectroscopic data, including 1D and 2D NMR, IR, HR-ESI-MS, and single-crystal X-ray diffraction analysis. The anti-insecticidal activities of these compounds were evaluated by contact toxicity tests against two-spotted spider mites, and compounds 1, 2, and 9 showed moderate contact toxicity, with LC50 values of 0.86±0.09, 0.95±0.23, and 0.89±0.19 mg/mL, respectively. This study highlights the potential use of diterpenoid alkaloids as natural plant-derived pesticides for the management of plant pests.

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Over the past decades, spin qubits in silicon carbide (SiC) have emerged as promising platforms for a wide range of quantum technologies. The fluorescence intensity holds significant importance in the performance of quantum photonics, quantum information process, and sensitivity of quantum sensing. In this work, a dual-layer Au/SiO2 dielectric cavity is employed to enhance the fluorescence intensity of a shallow silicon vacancy ensemble in 4H-SiC. Experimental results demonstrate an effective fourfold augmentation in fluorescence counts at saturating laser power, corroborating our theoretical predictions. Based on this, we further investigate the influence of dielectric cavities on the contrast and linewidth of optically detected magnetic resonance (ODMR). There is a 1.6-fold improvement in magnetic field sensitivity. In spin echo experiments, coherence times remain constant regardless of the thickness of dielectric cavities. These experiments pave the way for broader applications of dielectric cavities in SiC-based quantum technologies.

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The green and environmentally friendly cardanol epoxy resin has a bright application prospect, but its insufficient thermal/mechanical properties seriously hinder its application. Adding nanoclay to polymer matrix is an effective method to enhance the thermal/mechanical properties of material, but the dispersion and compatibility of nanoclay in epoxy resin remain to be solved. In this work, active Girard's reagent clay (PG-clay) and non-active Girard's reagent clay (NG-clay) were prepared by using acethydrazide trimethylammonium chloride (Girard's reagent) as the modifier, and cardanol epoxy resin/G-clay nanocomposites were synthesized by the "clay slurry composite method". The results showed that both PG-clay and NG-clay were dispersed in the epoxy matrix in the form of random exfoliation/intercalation, which effectively improved the thermal/mechanical properties of the composites. Tg of the cardanol epoxy resin has raised from 19.8 °C to 38.1 °C (4 wt.% PG-clay). When the mass fraction of clay is 4%, the tensile strength of the non-reactive NG-clay increases by 128%, and the elongation at break also increases by 101%. Simultaneously, the active PG-clay can participate in the curing reaction of epoxy resin due to the amino group, forming a chemical bond between the clay layer and the resin matrix and establishing a strong interfacial force. The tensile strength of the composite is increased by 970%, and the elongation at break is also increased by 428%. This research demonstrates that the cardanol epoxy resin/G-clay nanocomposite stands as a highly promising candidate for bio-based epoxy resin materials.

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A compact, low-loss, and high-polarized-extinction ratio TM-pass polarizer based on a graphene hybrid plasmonic waveguide (GHPW) has been demonstrated for the terahertz band. A ridge coated by a graphene layer and the hollow HPW with a semiround arch (SRA) Si core is introduced to improve structural compactness and suppress the loss. Based on this, a TM-pass polarizer has been designed that can effectively cut off the unwanted TE mode, and the TM mode passes with negligible loss. By optimizing the angle of the ridge, the height of the ridge, air gap height, and the length of the tapered mode converter, an optimum performance with a high polarization extinction ratio of 30.28 dB and a low insert loss of 0.4 dB is achieved in the 3 THz band. This work provides a scheme for the design and optimization of polarizers in the THz band, which has potential application value in integrated terahertz systems.

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OBJECTIVE: To observe the therapeutic effects and underlying mechanism of baicalin against colon cancer. METHODS: The effects of baicalin on the proliferation and growth of colon cancer cells MC38 and CT26. WT were observed and predicted potential molecular targets of baicalin for colon cancer therapy were studied by network pharmacology. Furthermore, molecular docking and drug affinity responsive target stability (DARTS) analysis were performed to confirm the interaction between potential targets and baicalin. Finally, the mechanisms predicted by in silico analyses were experimentally verified in-vitro and in-vivo. RESULTS: Baicalin significantly inhibited proliferation, invasion, migration, and induced apoptosis in MC38 and CT26 cells (all P<0.01). Additionally, baicalin caused cell cycle arrest at the S phase, while the G0/G1 phase was detected in the tiny portion of the cells. Subsequent network pharmacology analysis identified 6 therapeutic targets associated with baicalin, which potentially affect various pathways including 39 biological processes and 99 signaling pathways. In addition, molecular docking and DARTS predicted the potential binding of baicalin with cyclin dependent kinase inhibitor 2A (CDKN2A), protein kinase B (AKT), caspase 3, and mitogen-activated protein kinase (MAPK). In vitro, the expressions of CDKN2A, MAPK, and p-AKT were suppressed by baicalin in MC38 and CT26 cells. In vivo, baicalin significantly reduced the tumor size and weight (all P<0.01) in the colon cancer mouse model via inactivating p-AKT, CDKN2A, cyclin dependent kinase 4, cyclin dependent kinase 2, interleukin-1, tumor necrosis factor α, and activating caspase 3 and mouse double minute 2 homolog signaling (all P<0.05). CONCLUSION: Baicalin suppressed the CDKN2A protein level to prevent colon cancer and could be used as a therapeutic target for colon cancer.

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Inositol hexaphosphate (InsP6) is the major storage form of phosphorus in seeds. Reducing seed InsP6 content is a breeding objective in agriculture, as InsP6 negatively impacts animal nutrition and the environment. Nevertheless, how InsP6 accumulation is regulated remains largely unknown. Here, we identify a clade of receptor-like cytoplasmic kinases (RLCKs), named Inositol Polyphosphate-related Cytoplasmic Kinases 1-6 (IPCK1-IPCK6), deeply involved in InsP6 accumulation. The InsP6 concentration is dramatically reduced in seeds of ipck quadruple (T-4m/C-4m) and quintuple (C-5m) mutants, accompanied with the obviously increase of phosphate (Pi) concentration. The plasma membrane-localized IPCKs recruit IPK1 involved in InsP6 synthesis, and facilitate its binding and activity via phosphorylation of GRF 14-3-3 proteins. IPCKs also recruit IPK2s and PI-PLCs required for InsP4/InsP5 and InsP3 biosynthesis respectively, to form a potential IPCK-GRF-PLC-IPK2-IPK1 complex. Our findings therefore uncover a regulatory mechanism of InsP6 accumulation governed by IPCKs, shedding light on the mechanisms of InsP biosynthesis in eukaryotes.

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Background: Cervical intraepithelial neoplasia (CIN) encompasses a range of cervical lesions that are closely linked to cervical invasive carcinoma. Early detection and timely treatment of CIN are crucial for preventing the progression of the disease. However, no bibliometric analysis has been conducted in this area. This research aimed to employ bibliometric analysis to summarize the current research hotspots and estimate future research trends in the CIN field. Methods: Publications related to CIN (2013-2023) were retrieved from the Science-Citation-Index-Expanded-of-Web-of-Science-Core-Collection. CiteSpace, VOSviewer, and the bibliometric-Online-Analysis-Platform-of-Literature-Metrology were employed to analyze the yearly research output, collaborating institutions or countries, leading researchers, principal journals, co-referenced sources, and emerging keywords. Results: In total, 4677 articles on CIN that were published from 2013 to 2023 and met our criteria were extracted. Major publishing platforms were predominantly USA until 2017 when China emerged as the leading source of publications about CIN. The USA was the leading nation in international collaborations. The National-Cancer-Institute (NCI) was the institution with the most publications. Schiffman Mark produced the highest number of articles, with a total of 92. Ten major clusters were identified through co-cited keyword clustering, including prevalence, human papillomavirus, DNA methylation, p16, methylation, conization, HPV genotyping tests (VALGENT), deep learning, vaginal microbiome, and immunohistochemistry. Keyword burst analysis showed that photodynamic therapy and deep learning emerged as prominent research focal points with significant impact in resent three years. Conclusion: Global publications on CIN research showed a relatively stable trend over the past eleven years. Current research hotspots are deep learning and photodynamic therapy. This research offered organized data and insightful guidance for future studies, which may help better prevent, screen, and treat CIN.