Target deubiquitinase OTUB1 as a therapeatic strategy for BLCA via ß-catenin/necroptosis signal pathway.

Ubiquitination, a prevalent and highly dynamic reversible post-translational modification, is tightly regulated by the deubiquitinating enzymes (DUBs) superfamily. Among them, OTU Domain-Containing Ubiquitin Aldehyde-Binding Protein 1 (OTUB1) stands out as a critical member of the OTU deubiquitinating family, playing a pivotal role as a tumor regulator across various cancers. However, its specific involvement in BLCA (BLCA) and its clinical significance have remained ambiguous. This study aimed to elucidate the biofunctions of OTUB1 in BLCA and its implications for clinical prognosis. Our investigation revealed heightened OTUB1 expression in BLCA, correlating with unfavorable clinical outcomes. Through in vivo and in vitro experiments, we demonstrated that increased OTUB1 levels promote BLCA tumorigenesis and progression, along with conferring resistance to cisplatin treatment. Notably, we established a comprehensive network involving OTUB1, ß-catenin, necroptosis, and BLCA, delineating their regulatory interplay. Mechanistically, we uncovered that OTUB1 exerts its influence by deubiquitinating and stabilizing ß-catenin, leading to its nuclear translocation. Subsequently, nuclear ß-catenin enhances the transcriptional activity of c-myc and cyclin D1 while suppressing the expression of RIPK3 and MLKL, thereby fostering BLCA progression and cisplatin resistance. Importantly, our clinical data suggest that the OTUB1/ß-catenin/RIPK3/MLKL axis holds promise as a potential biomarker for BLCA.

Highly selective photocatalytic CO2 reduction into C2H4 enabled by metal-organic framework-derived catalysts with high Cu+ content.

The highly selective conversion of CO2 into valuable C2H4 is a highly important but particularly challenging reaction. Herein, the metal-organic frameworks MOF-74(Cu) with infinite Cu(II)-O chains and Cu-BTC (BTC=benzene-1,3,5-tricarboxylate) with paddle-wheel binuclear Cu(II) clusters are used as precursors. These MOFs are reduced by NaBH4 to obtain Cu0/Cuδ+-based photocatalysts denoted as R-MOF-74(Cu) and R-Cu-BTC, respectively. Significantly, R-MOF-74(Cu) achieves a high selectivity of 90.2 % for C2H4 with a yield rate of 6.5 µmol g-1 within 5 h due to its high Cu+ content. To the best of our knowledge, this C2H4 product selectivity is a record high among all the photocatalysts reported so far for photocatalytic CO2 reduction. In contrast, R-Cu-BTC only forms CO as a product with a cumulative yield of 0.7 µmol g-1 within 5 h. Photoelectrochemical characterization and electron paramagnetic resonance results show that R-MOF-74(Cu) has low interfacial transfer resistance, high photogenerated electron separation efficiency, and excellent CO2 activation and water oxidation performance. In addition, in situ Fourier transform infrared spectroscopy is used to determine the possible reaction pathway from CO2 to C2H4 over R-MOF-74(Cu). This work demonstrates the great potential of MOF-derived photocatalysts for the conversion of CO2 into C2H4 and provides guidance for future photocatalyst development.

Elevated triglyceride-glucose index associated with increased risk of diabetes in non-obese young adults: a longitudinal retrospective cohort study from multiple Asian countries.

Objective: Previous studies have confirmed a positive correlation between the Triglyceride-Glucose (TyG) index and future risk of diabetes. However, evidence of this association in non-obese young populations remains limited. This study aims to investigate the relationship between the TyG index and the future risk of diabetes among non-obese young adults. Methods: This retrospective cohort study included 113,509 non-obese young adults from China and 9,549 from Japan. The mean age was 35.73 ± 6.38 years, and 56,469 participants (45.89%) were male. The median follow-up duration was 3.38 years. The association between baseline TyG index and risk of diabetes was examined using Cox proportional hazards regression models. Non-linear relationships between the TyG index and risk of diabetes were identified using cubic splines and smoothed curve fitting in the Cox models. Sensitivity and subgroup analyses were also conducted. Results: After adjusting for covariates, the results indicated a positive correlation between the TyG index and risk of diabetes in non-obese young adults (HR=3.57, 95% CI: 2.92-4.36, P<0.0001). A non-linear relationship was observed with an inflection point at 7.3. The HR to the right of this inflection point was 3.70 (95% CI: 3.02-4.52, P<0.0001), while to the left, it was 0.34 (95% CI: 0.06-1.88, P=0.2161). The robustness of our findings was confirmed through a series of sensitivity analyses and subgroup analyses. Conclusion: This study reveals a positive and non-linear association between the TyG index and risk of diabetes among non-obese young adults. Interventions aimed at reducing the TyG index by lowering triglycerides or fasting glucose levels could substantially decrease the future likelihood of developing diabetes in this population.

Molecular insight into oil displacement by CO2 flooding in water-cut dead-end nanopores.

Understanding the mechanisms underlying residual oil displacement by CO2 flooding is essential for CO2-enhanced oil recovery. This study utilizes molecular dynamics (MD) simulations to investigate the displacement of residual oil by CO2 flooding in dead-end nanopores, focusing specifically on the water-blocking effect. The findings reveal that oil displacement does not commence until the water film is breached. The dissolution of CO2 molecules in water and the hydrogen bond interactions between water and rock are the primary factors that disrupt the hydrogen bond network among the water molecules, facilitating the breakthrough of the water film. Additionally, the displacement process can be delineated into four distinct stages - encompassing water film rupture, oil swelling, massive oil displacement, and displacement completion - as evidenced by the oil recovery-displacement time curves. Moreover, a cutting-edge oil recovery-displacement time model precisely quantifies crucial stages in the displacement process. For example, when t < δ, trapped oil is impeded by the water film, while when t > δ + 3τ, displacement culminates successfully. Altogether, this research bolsters comprehension of residual oil displacement in the presence of water blocking and advocates for sustainable oil production strategies in oilfields.

Comprehensive analysis of the association between triglyceride-glucose index and coronary artery disease severity across different glucose metabolism states: a large-scale cross-sectional study from an Asian cohort.

BACKGROUND: The triglyceride-glucose (TyG) index is associated with the development and prognosis of coronary artery disease (CAD). However, the impact of the TyG index on CAD severity across different glucose metabolism states exhibits significant disparities in previous research. METHODS: This cross-sectional study comprised 10,433 participants from a prospective cohort. Participants were categorized into four groups based on glucose metabolism state: normal glucose regulation (NGR), prediabetes (pre-DM), diabetes mellitus (DM) without insulin prescribed (Rx), and DM with insulin Rx. The TyG index was determined by the following formula: Ln [TG (mg/dL) × FPG (mg/dL) / 2], where TG is triglycerides and FPG is fasting plasm glucose. Statistical methods such as binary logistic regression, interaction analysis, restricted cubic spline (RCS), and receiver operating characteristic (ROC) were employed to analyze the relationship between the TyG index and CAD severity across the entire population and glucose metabolism subgroups. Mediation analysis was conducted to examine the mediating effects of glycated hemoglobin (HbA1c) on these relationships. Sensitivity analysis was performed to ensure the robustness of the findings. RESULTS: Multivariable logistic regression analysis revealed a significant positive association between the TyG index and multi-vessel CAD in the entire population (OR: 1.34; 95% CI: 1.22-1.47 per 1-unit increment). Subgroup analysis demonstrated consistent positive associations in the NGR, pre-DM, and DM non-insulin Rx groups, with the highest OR observed in the NGR group (OR: 1.67; 95% CI: 1.3-2.14 per 1-unit increment). No correlation was found in the DM with insulin Rx subgroup. RCS analyses indicated the distinct dose-response relationships across different glucose metabolism subgroups. Including the TyG index in the established model slightly improved the predictive accuracy, particularly in the NGR group. Mediation analyses showed varying mediating effects of HbA1c among different glucose metabolism subgroups. Sensitivity analysis confirmed the robustness of the aforementioned relationships in the new-onset CAD population and in individuals not using antilipidemic medications. CONCLUSIONS: The TyG index positively associated with CAD severity across all glucose metabolism states, except for individuals receiving insulin treatment. Moreover, it might serve as a supplementary noninvasive predictor of CAD severity in addition to established factors, especially in NGR patients.

Hydroxypropyl methylcellulose reinforced bilayer hydrogel dressings containing L-arginine-modified polyoxometalate nanoclusters to promote healing of chronic diabetic wounds.

Diabetes-related slow healing of wounds is primarily driven by bacterial infections and angiogenesis disorder and presents a substantial hurdle in clinical treatment. To solve the above problems, an advanced multifunctional hydrogel system based on natural polymer was created here to facilitate wound healing in patients with chronic diabetes. The prepared dressing was composed of an outer hydrogel containing polyvinyl alcohol and hydroxypropyl methyl cellulose in dimethyl sulfoxide and water as binary solvents, and an inner hydrogel containing chitosan quaternary ammonium salt, flaxseed gum, and polyvinyl alcohol. Thus, a polysaccharide based bilayer hydrogel (BH) with superior mechanical strength and biocompatibility was created. This bilayer hydrogel could easily bind to dynamic tissue surfaces, thereby generating a protective barrier. Meanwhile, L-arginine-modified polyoxometalate (POM@L-Arg) nanoclusters were loaded in the inner hydrogel. They released NO when stimulated by the peroxide microenvironment of diabetic wounds. NO as a signal molecule regulated vascular tension and promoted cell proliferation and migration. Additionally, because of the synergistic effect of NO and the chitosan quaternary ammonium salt, the hydrogel system exhibited excellent antibacterial performance. The NO released reduced the levels of proinflammatory factors IL-6 and TNF-α in the diabetic wounds, which thus accelerated wound healing. In short, BH + POM@L-Arg is expected to serve as an ideal wound dressing as it exerts a good promotion effect on diabetes-related wound healing.

An injectable hydrogel based on sodium alginate and gelatin treats bacterial keratitis through multimodal antibacterial strategy.

Bacterial keratitis is among the most prevalent causes of blindness. Currently, the abuse of antibiotics in clinical settings not only lacks bactericidal effects but also readily induces bacterial resistance, making the clinical treatment of bacterial keratitis a significant challenge. In this study, we present an injectable hydrogel (GS-PNH-FF@CuS/MnS) containing self-assembled diphenylalanine dipeptide (FF) and CuS/MnS nanocomposites (CuS/MnS NCs) that destroy bacterial cell walls through a synergistic combination of mild photothermal therapy (PTT), chemodynamic therapy (CDT), ion release chemotherapy, and self-assembled dipeptide contact, thereby eliminating Pseudomonas aeruginosa. Under 808 nm laser irradiation, the bactericidal efficiency of GS-PNH-FF@CuS/MnS hydrogel against P. aeruginosa in vitro reach up to 96.97 %. Furthermore, GS-PNH-FF@CuS/MnS hydrogel is applied topically to kill bacteria, reduce inflammation, and promote wound healing. Hematoxylin-eosin (H&E) staining, Masson staining, immunohistochemistry and immunofluorescence staining are used to evaluate the therapeutic effect on infected rabbit cornea models in vivo. The GS-PNH-FF@CuS/MnS demonstrate good biocompatibility with human corneal epithelial cells and exhibit no obvious eyes side effects. In conclusion, the GS-PNH-FF@CuS/MnS hydrogel in this study provides an effective and safe treatment strategy for bacterial keratitis through a multimodal approach.

FedKG: A Knowledge Distillation-Based Federated Graph Method for Social Bot Detection.

Malicious social bots pose a serious threat to social network security by spreading false information and guiding bad opinions in social networks. The singularity and scarcity of single organization data and the high cost of labeling social bots have given rise to the construction of federated models that combine federated learning with social bot detection. In this paper, we first combine the federated learning framework with the Relational Graph Convolutional Neural Network (RGCN) model to achieve federated social bot detection. A class-level cross entropy loss function is applied in the local model training to mitigate the effects of the class imbalance problem in local data. To address the data heterogeneity issue from multiple participants, we optimize the classical federated learning algorithm by applying knowledge distillation methods. Specifically, we adjust the client-side and server-side models separately: training a global generator to generate pseudo-samples based on the local data distribution knowledge to correct the optimization direction of client-side classification models, and integrating client-side classification models' knowledge on the server side to guide the training of the global classification model. We conduct extensive experiments on widely used datasets, and the results demonstrate the effectiveness of our approach in social bot detection in heterogeneous data scenarios. Compared to baseline methods, our approach achieves a nearly 3-10% improvement in detection accuracy when the data heterogeneity is larger. Additionally, our method achieves the specified accuracy with minimal communication rounds.

Effects of Nitrogen Application at Different Levels by a Sprinkler Fertigation System on Crop Growth and Nitrogen-Use Efficiency of Winter Wheat in the North China Plain.

Nitrogen (N) is an essential macronutrient for crop growth; therefore, N deficit can greatly limit crop growth and production. In the North China Plain (NCP), winter wheat (Triticum aestivum L.) is one of the main food crops, and its yield has increased from approximately 4000 kg ha-1 to 6000 kg ha-1 in the last two decades. Determining the proper N application rates at different growth stages and in all seasons is very important for the sustainable and high production of wheat in the NCP. A field experiment with five N application rates (250, 200, 150, 100, and 40 kgN·ha-1, designated as N250, N200, N150, N100, and N40, respectively) was conducted during the 2017-2018 and 2018-2019 winter wheat seasons to investigate the effects of the N application rate on water- and fertilizer-utilization efficiency and on the crop growth and yield of winter wheat under sprinkler fertigation conditions. The results showed that in the N application range of 40-200 kg ha-1, crop yield and water- and fertilizer-use efficiencies increased as the N application rate increased; however, further increases in the N application rate (from N200 to N250) did not have additional benefits. The N uptake after regreening of winter wheat linearly increased with crop growth. Considering the wheat yield and N-use efficiency, the recommended optimal N application rate was 200 kg ha-1, and the best topdressing strategy was equal amounts of N applied at the regreening, jointing, and grain-filling stages. The results of this study will be useful for optimizing field N management to achieve high wheat yield production in the NCP and in regions with similar climatic and soil environment conditions.

Association of the stress hyperglycemia ratio with coronary artery disease complexity as assessed by the SYNTAX score in patients with acute coronary syndrome.

BACKGROUND: Mounting evidence supports a significant correlation between the stress hyperglycemia ratio (SHR) and both short- and long-term prognoses in patients with acute coronary syndrome (ACS). Nevertheless, research examining the association between the SHR and the complexity of coronary artery disease (CAD) is scarce. Therefore, this study aimed to explore the association between the SHR and CAD complexity, as assessed by the SYNTAX score, in patients with ACS. METHODS: A total of 4715 patients diagnosed with ACS were enrolled and divided into five groups according to the quintiles of the SHR. CAD complexity was assessed using the SYNTAX score and categorized as low (≤ 22) or mid/high (> 22) levels. Logistic regression was utilized to examine the association between the SHR and CAD severity (mid-/high SYNTAX score). Restricted cubic spline (RCS) curves were generated to assess the association between the SHR and CAD severity. Subgroup analyses were conducted to stratify outcomes based on age, sex, diabetes mellitus (DM) status, and clinical presentation. RESULTS: Among the total ACS population, 503 (10.7%) patients had mid/high SYNTAX scores. Logistic regression analysis revealed that the SHR was an independent risk factor for mid/high SYNTAX scores in a U-shaped pattern. After adjusting for confounding variables, Q1 and Q5 demonstrated elevated odds ratios (ORs) relative to the reference category Q3, with ORs of 1.61 (95% CI: 1.19 ∼ 2.19) and 1.68 (95% CI: 1.24 ∼ 2.29), respectively. Moreover, the ORs for Q2 (1.02, 95% CI: 0.73 ∼ 1.42) and Q4 (1.18, 95% CI: 0.85 ∼ 1.63) resembled that of Q3. Compared with the merged Q2-4 group, the ORs were 1.52 (95% CI: 1.21 ∼ 1.92) for Q1 group and 1.58 (95% CI: 1.25 ∼ 2) for the Q5 group. Subgroup analysis revealed that the U-shaped association between the SHR and mid/high SYNTAX score was attenuated in DM patients (P for interaction = 0.045). CONCLUSIONS: There were U-shaped associations between the SHR and CAD complexity in ACS patients, with an SHR ranging from 0.68 to 0.875 indicating a relatively lower OR for mid/high SYNTAX scores. Further studies are necessary to both evaluate the predictive value of the SHR in ACS patients and explore the underlying mechanisms of the observed U-shaped associations.

Acceleration of Photoinduced Electron Transfer by Modulating Electronegativity of Substituents in Stable Zr-Metal-Organic Frameworks to Boost Photocatalytic CO2 Reduction.

Photoreduction of CO2 with water into chemical feedstocks of fuels provides a green way to help solve both the energy crisis and carbon emission issues. Metal-organic frameworks (MOFs) show great potential for CO2 photoreduction. However, poor water stability and sluggish charge transfer could limit their application. Herein, three water-stable MOFs functionalized with electron-donating methyl groups and/or electron-withdrawing trifluoromethyl groups are obtained for the CO2 photoreduction. Compared with UiO-67-o-CF3-CH3 and UiO-67-o-(CF3)2, UiO-67-o-(CH3)2 achieves excellent performance with an average CO generation rate of 178.0 µmol g-1 h-1 without using any organic solvent or sacrificial reagent. The superior photocatalytic activity of UiO-67-o-(CH3)2 is attributed to the fact that compared with trifluoromethyl groups, methyl groups could not only elevate CO2 adsorption capacity and reduction potential but also promote photoinduced charge separation and migration. These are evidenced by gas physisorption, photoluminescence, time-resolved photoluminescence, electrochemical impedance spectroscopy, transient photocurrent characteristics, and density functional theory calculations. The possible working mechanisms of electron-donating methyl groups are also proposed. Moreover, UiO-67-o-(CH3)2 demonstrates excellent reusability for the CO2 reduction. Based on these results, it could be affirmed that the strategy of modulating substituent electronegativity could provide guidance for designing highly efficient photocatalysts.

Forsythiaside-A improved bile-duct-ligation-induced liver fibrosis in mice: The involvement of alleviating mitochondrial damage and ferroptosis in hepatocytes via activating Nrf2.

Liver fibrosis is a key and reversible stage in the progression of many chronic liver diseases to cirrhosis or hepatocellular carcinoma. Forsythiaside-A (FTA), a main compound isolated from Forsythiae Fructus, has an excellent liver protective activity. This study aims to investigate the efficacy of FTA in improving cholestatic liver fibrosis. Bile-duct-ligation (BDL) was conducted to induce liver fibrosis in mice. Hepatic collagen deposition was evaluated by Masson and Sirus red staining. The bile acid spectrum in the liver and serum was analyzed by mass spectrometry. Liver oxidative stress injury and mitochondria damage were observed by using Mito-Tracker Red fluorescence staining, transmission electron microscopy, etc. The level of ferrous iron (Fe2+) and the expression of ferroptosis-associated molecules were detected. The binding between FTA and its target protein was confirmed by Co-immunoprecipitation (Co-IP), cellular thermal shift assay (CETSA), drug affinity responsive target stability (DARTS) and surface plasmon resonance (SPR). Our results demonstrated that FTA alleviated BDL-induced liver fibrosis in mice. FTA did not decrease the elevated amount of bile acids in BDL-treated mice, but reduced the bile acid-induced mitochondrial damage, oxidative stress and ferroptosis in hepatocytes, and also induced nuclear factor erythroid 2-related factor-2 (Nrf2) activation. In Nrf2 knock-out mice, the FTA-provided protection against BDL-induced liver fibrosis was disappeared, and FTA's inhibition on mitochondrial damage, oxidative stress and ferroptosis were lowered. Further results displayed that FTA could directly bind to Kelch-like ECH-associated protein-1 (Keap1), thereby activating Nrf2. Moreover, the BDL-induced liver fibrosis was markedly weakened in liver-specific Keap1 knockout mice. Hence, this study suggests that FTA alleviated the BDL-induced liver fibrosis through attenuating mitochondrial damage and ferroptosis in hepatocytes by activating Nrf2 via directly binding to Keap1.

The combination of berberine and isoliquiritigenin synergistically improved adipose inflammation and obesity-induced insulin resistance.

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

In Situ Construction of CuTCPP/Bi4O5Br2 Hybrids for Improved Photocatalytic CO2 and Cr(VI) Reduction.

Global warming and heavy metal pollution pose tremendous challenges to human development, and photocatalysis is considered to be an effective strategy to solve these problems. Herein, copper(II) tetra (4-carboxyphenyl) porphyrin (CuTCPP) molecules were successfully in situ loaded onto Bi4O5Br2 by a hydrothermal approach. A series of experimental results show that the light absorption capacity and photogenerated carrier separation efficiency were synchronously enhanced after the construction of CuTCPP/Bi4O5Br2 composites. Hence, the as-prepared composites possess significantly improved photocatalytic ability for both CO2 and Cr(VI) reduction. Specifically, CuTCPP/Bi4O5Br2-2 achieves a CO generation rate of 17.14 µmol g-1 under 5 h irradiation, which is twice as high as that of Bi4O5Br2 (8.57 µmol g-1). Besides, the optimized CuTCPP/Bi4O5Br2-2 also exhibits a removal rate of 61.87% for Cr(VI) within 100 min under irradiation. Furthermore, the mechanism of CO2 and Cr(VI) photoreduction was explored by in situ Fourier transform infrared spectroscopy and capture experiments, respectively. This work can be a reference toward the construction of photocatalysts with high activity for solar energy conversion.

Single-atom nickel sites boosting Si nanowires for photoelectrocatalytic CO2 conversion with nearly 100% selectivity.

It is a challenge to design a photocathode with well-defined active sites for efficient photoelectrocatalytic CO2 reduction. Herein, single-atom Ni sites are integrated into Si nanowires to develop a novel photocathode, denoted as Ni-NC/Si. The photocathode demonstrates a stable faradaic efficiency for CO production, approaching nearly 100% at -0.6 V vs. RHE. The introduction of single-atom Ni sites provides sufficient active sites for CO2 reduction, thereby improving the selectivity towards CO formation.

Platelet-derived microparticles and their cargos: The past, present and future.

All eukaryotic cells can secrete extracellular vesicles, which have a double-membrane structure and are important players in the intercellular communication involved in a variety of important biological processes. Platelets form platelet-derived microparticles (PMPs) in response to activation, injury, or apoptosis. This review introduces the origin, pathway, and biological functions of PMPs and their importance in physiological and pathological processes. In addition, we review the potential applications of PMPs in cancer, vascular homeostasis, thrombosis, inflammation, neural regeneration, biomarkers, and drug carriers to achieve targeted drug delivery. In addition, we comprehensively report on the origin, biological functions, and applications of PMPs. The clinical transformation, high heterogeneity, future development direction, and limitations of the current research on PMPs are also discussed in depth. Evidence has revealed that PMPs play an important role in cell-cell communication, providing clues for the development of PMPs as carriers for relevant cell-targeted drugs. The development history and prospects of PMPs and their cargos are explored in this guidebook.

Identification of hub genes within the CCL18 signaling pathway in hepatocellular carcinoma through bioinformatics analysis.

Introduction: Hepatocellular carcinoma (HCC) is an aggressive malignancy, and CCL18, a marker of M2 macrophage activation, is often associated with tumor immune suppression. However, the role of CCL18 and its signaling pathway in HCC is still limited. Our study focuses on investigating the prognostic impact of CCL18 and its signaling pathway in HCC patients and biological functions in vitro. Methods: HCC-related RNA-seq data were obtained from TCGA, ICGC, and GEO. The 6 hub genes with the highest correlation to prognosis were identified using univariate Cox and LASSO regression analysis. Multivariate Cox regression analysis was performed to assess their independent prognostic potential and a nomogram was constructed. In vitro experiments, including CCK8, EdU, RT-qPCR, western blot, and transwell assays, were conducted to investigate the biological effects of exogenous CCL18 and 6 hub genes. A core network of highly expressed proteins in the high-risk group of tumors was constructed. Immune cell infiltration was evaluated using the ESTIMATE and CIBERSORT packages. Finally, potential treatments were explored using the OncoPredict package and CAMP database. Results: We identified 6 survival-related genes (BMI1, CCR3, CDC25C, CFL1, LDHA, RAC1) within the CCL18 signaling pathway in HCC patients. A nomogram was constructed using the TCGA_LIHC cohort to predict patient survival probability. Exogenous CCL18, as well as overexpression of BMI1, CCR3, CDC25C, CFL1, LDHA, and RAC1, can promote proliferation, migration, invasion, stemness, and increased expression of PD-L1 protein in LM3 and MHCC-97H cell lines. In the high-risk group of patients from the TCGA_LIHC cohort, immune suppression was observed, with a strong correlation to 21 immune-related genes and suppressive immune cells. Conclusion: Exogenous CCL18 promotes LM3 and MHCC-97H cells proliferation, migration, invasion, stemness, and immune evasion. The high expression of BMI1, CCR3, CDC25C, CFL1, LDHA, and RAC1 can serve as a biomarkers for immune evasion in HCC.

Pseudohalogen Ammonium Salt-Assisted Syntheses of Large-Sized Indium Phosphide Quantum Dots with Near-Infrared Photoluminescence.

The development of indium phosphide (InP)-based quantum dots (QDs) with a near-infrared (NIR) emission area still lags behind the visible wavelength region and remains problematic. This study describes a one-step in situ pseudohalogen ammonium salt-assisted approach to generate NIR-emitted InP-based QDs with high photoluminescence quantum yields (PLQYs). The coexistence of NH4+ and PF6- ions from NH4PF6 may in situ synchronously etch and passivate the surface oxides and impede the creation of traps under the whole growth process of InP QDs. Experimental findings demonstrated that the in situ pseudohalogen ammonium salt-assisted syntheses technique may feature emission at a full width at half-maximum (fwhm) peak as fine as ∼45 nm and broaden the emission range to around ∼780 nm. A two-step approach for ZnS shells was developed to further improve the PLQY of NIR-emitted InP QDs. Furthermore, the constructed high-power intrinsically stretchable NIR color-conversion film employing the InP-based QDs/polymer composites presented excellent luminescence conversion ability and stretchability.

Surface Passivation toward Multiple Inherent Dangling Bonds in Indium Phosphide Quantum Dots.

Indium phosphide (InP) quantum dots (QDs) have become the most recognized prospect to be less-toxic surrogates for Cd-based optoelectronic systems. Due to the particularly dangling bonds (DBs) and the undesirable oxides, the photoluminescence performance and stability of InP QDs remain to be improved. Previous investigations largely focus on eliminating P-DBs and resultant surface oxidation states; however, little attention has been paid to the adverse effects of the surface In-DBs on InP QDs. This work demonstrates a facile one-step surface peeling and passivation treatment method for both In- and P-DBs for InP QDs. Meanwhile, the surface treatment may also effectively support the encapsulation of the ZnSe shell. Finally, the generated InP/ZnSe QDs display a narrower full width at half-maximum (fwhm) of ∼48 nm, higher photoluminescence quantum yields (PLQYs) of ∼70%, and superior stability. This work enlarges the surface chemistry engineering consideration of InP QDs and considerably promotes the development of efficient and stable optoelectronic devices.

Modified Internal Pudendal Artery Perforator Flap Interposition for Rectovaginal Fistula.

IMPORTANCE: Rectovaginal fistula (RVF) is a challenging condition associated with recurrences and significant functional impairment. OBJECTIVES: The internal pudendal artery perforator (IPAP) flap has become a viable option for reconstructing the vagina and perineal regions. This study aims to introduce a modified technique of IPAP flap interposition and evaluate its postoperative outcomes in the treatment of low RVF. STUDY DESIGN: Sixteen patients with RVF who underwent modified IPAP flap interposition between 2016 and 2021 were retrospectively enrolled. Recurrence rate, the satisfaction of vulvar appearance (Visual Analog Scale), and quality of sexual life (Female Sexual Function Index score) were followed up and analyzed. RESULTS: All patients presented with low fistula with a mean diameter of 8.3 mm. The mean width and length of the IPAP flaps were 3.8 and 6.2 cm, respectively. The mean follow-up period was 14.1 months. All patients achieved successful healing without recurrence. High satisfaction was reported for the cosmetic effect of the vulva with a mean Visual Analog Scale score of 8.4. The proportion of female sexual disorder exhibited a statistically significant reduction, decreasing from 100% preoperatively to 38% after surgery ( P < 0.05). CONCLUSIONS: The modified IPAP flap interposition is a reliable and safe option for repairing low RVF, with high success rates and minimal donor site morbidity. Moreover, this procedure provides a suitable volume flap and preserves the vaginal physiological environment, which benefits postoperative sexual function.