Natural tea polyphenol functionalized graphene anode for simultaneous power production and degradation of methyl orange dye in microbial fuel cells.

The microbial fuel cell (MFCs) has dual functions, capable of achieving dye decolorization and synchronous power generation. Despite these advantages, the MFCs have faced challenges related to low electron transfer efficiencies and limited dye treatment capacity in wastewater applications. This work introduces an innovative approach by employing reduced graphene oxide-modified carbon cloth (TP-RGO@CC) anodes, utilizing tea polyphenols as the reducing agent. This modification significantly enhances the hydrophilicity and biocompatibility of the anodes. The MFC equipped with the TP-RGO@CC anode demonstrated a remarkable increase in the maximum power density, reaching 773.9 mW m-2, representing a 22% improvement over the plain carbon cloth electrode. The decolorization rate of methyl orange (50 mg L-1, pH 7) reached 99% within 48 h. Biodiversity analysis revealed that the TP-RGO@CC anode selectively enriched electrogens producing and organic matter-degrading bacteria, promoting a dual mechanism of dye decolorization, degradation, and simultaneous electro-production at the anode. This work highlights advanced anode materials that excel in effective pollutant removal, energy conversion, and biomass reuse.

Establishing subdivisions of M1 stage nasopharyngeal carcinoma based on decision tree classification: A multicenter retrospective study.

OBJECTIVES: To meet the demand for personalized treatment, effective stratification of patients with metastatic nasopharyngeal carcinoma (mNPC) is essential. Hence, our study aimed to establish an M1 subdivision for prognostic prediction and treatment planning in patients with mNPC. MATERIALS AND METHODS: This study included 1239 patients with mNPC from three medical centers divided into the synchronous mNPC cohort (smNPC, n = 556) to establish an M1 stage subdivision and the metachronous mNPC cohort (mmNPC, n = 683) to validate this subdivision. The primary endpoint was overall survival. Univariate and multivariate Cox analyses identified covariates for the decision-tree model, proposing an M1 subdivision. Model performance was evaluated using time-dependent receiver operating characteristic curves, Harrell's concordance index, calibration plots, and decision curve analyses. RESULTS: The proposed M1 subdivisions were M1a (≤5 metastatic lesions), M1b (>5 metastatic lesions + absent liver metastases), and M1c (>5 metastatic lesions + existing liver metastases) with median OS of 34, 22, and 13 months, respectively (p < 0.001). This M1 subdivision demonstrated superior discrimination (C-index = 0.698; 3-year AUC = 0.707) and clinical utility over those of existing staging systems. Calibration curves exhibited satisfactory agreement between predictions and actual observations. Internal and mmNPC cohort validation confirmed the robustness. Survival benefits from local metastatic treatment were observed in M1a, while immunotherapy improved survival in patients with M1b and M1c disease. CONCLUSION: This novel M1 staging strategy provides a refined approach for prognostic prediction and treatment planning in patients with mNPC, emphasizing the potential benefits of local and immunotherapeutic interventions based on individualized risk stratification.

Characteristics of zero-valent iron surface oxide films under the catalytic interface reactions by assisting ligands in nitrate-contaminated groundwater.

The surface passivation layer coating on zero-valent iron (ZVI) particles impedes the electron transfer from ZVI to nitrate. To enhance the efficiency of nitrate reduction by Fe(0), we tested the chemical process and the thickness of the iron oxide film on the surface of Fe(0) particles, utilizing Fe2+aq in aqueous solution and wheat straw as ligands. A novel principal surface catalyzing reaction was formulated as follows: [Formula: see text] . When Fe2+aq concentration increased from 0 - 200 mg·L-1, the NO3- removal rate increased from 6.95% to 82.6% respectively during 12 h and it was 48%, 72%, 79% and 94% respectively in Fe0/WS ratio of 0, 0.25, 0.5 and 1 system. Uniform surface iron oxide films formed around the Fe(0) particles within 12 h after the adding Fe2+aq or wheat straw to the Fe(0) system. The composition and thickness of these films were dependent on the quantity of added materials. X-ray diffraction (XRD) analysis revealed that surface oxide iron mainly consisted of Fe2+ or Fe3+ oxides, with Fe3O4 being predominant. The X-ray photoelectron spectroscopy (XPS) etching indicated that the addition of Fe(0)/straw at mass ratios of 1 or system with 20 mg·L-1 Fe2+aq resulted in the thinnest surface iron oxide layer. The study demonstrated that reducing the oxide layer's thickness was achieved through partial catalysis and enhanced complexation capacity. This reduction was facilitated by the introduction of Fe2+aq or wheat straw into the Fe(0) system, potentially improving proton dissociation and promoting the ligand-assisted dissolution of Fe3+ oxides.

Acidification of α-granules in megakaryocytes by vacuolar-type ATPase is essential for organelle biogenesis.

BACKGROUND: Platelets coordinate blood coagulation at sites of vascular injury and play fundamental roles in a wide variety of (patho)physiological processes. Key to many platelet functions is the transport and secretion of proteins packaged within α-granules, organelles produced by platelet precursor megakaryocytes. Prominent among α-granule cargo are fibrinogen (FGN) endocytosed from plasma, and endogenously-synthesized Von Willebrand factor (VWF). These and other proteins are known to require acidic pH for stable packaging. Luminal acidity has been confirmed for mature α-granules isolated from platelets, but direct measurement of megakaryocyte granule acidity has not been reported. OBJECTIVE: To determine the luminal pH of α-granules and their precursors in megakaryocytes, and assess the requirement of vacuolar-type adenosine triphosphatase (V-ATPase) activity establish and maintain the luminal acidity and integrity of these organelles. RESULTS: Using cresyl violet staining, we show that most of the acidic granules detected in megakaryocytes appear to be α-granules/precursors. Endocytosis of FGN tagged with the pH-sensitive fluorescent dye FITC was used to load a subset of these organelles, and ratiometric fluorescence analysis established a median luminal pH of 5.2 (interquartile range 5.0 - 5.5). Inhibition of megakaryocyte V-ATPase activity led to enlargement of cargo-containing compartments detected by fluorescence microscopy and electron microscopy. CONCLUSION: These observations reveal that V-ATPase activity is required to establish and maintain a luminal acidic pH in megakaryocyte α-granules/precursors, confirming its importance for stable packaging of cargo proteins such as VWF.

AURKB promotes colorectal cancer progression by triggering the phosphorylation of histone H3 at serine 10 to activate CCNE1 expression.

Aurora kinase B (AURKB) initiates the phosphorylation of serine 10 on histone H3 (pH3S10), a crucial process for chromosome condensation and cytokinesis in mammalian mitosis. Nonetheless, the precise mechanisms through which AURKB regulates the cell cycle and contributes to tumorigenesis as an oncogenic factor in colorectal cancer (CRC) remain unclear. Here, we report that AURKB was highly expressed and positively correlated with Ki-67 expression in CRC. The abundant expression of AURKB promotes the growth of CRC cells and xenograft tumors in animal model. AURKB knockdown substantially suppressed CRC proliferation and triggered cell cycle arrest in G2/M phase. Interestingly, cyclin E1 (CCNE1) was discovered as a direct downstream target of AURKB and functioned synergistically with AURKB to promote CRC cell proliferation. Mechanically, AURKB activated CCNE1 expression by triggering pH3S10 in the promoter region of CCNE1. Furthermore, it was showed that the inhibitor specific for AURKB (AZD1152) can suppress CCNE1 expression in CRC cells and inhibit tumor cell growth. To conclude, this research demonstrates that AURKB accelerated the tumorigenesis of CRC through its potential to epigenetically activate CCNE1 expression, suggesting AURKB as a promising therapeutic target in CRC.

Exploring in vivo combinatorial chemo-immunotherapy: Addressing p97 suppression and immune reinvigoration in pancreatic cancer with tumor microenvironment-responsive nanoformulation.

Pancreatic ductal adenocarcinoma (PDAC) has an extremely devastating nature with poor prognosis and increasing incidence, making it a formidable challenge in the global fight against cancer-related mortality. In this innovative preclinical investigation, the VCP/p97 inhibitor CB-5083 (CB), miR-142, a PD-L1 inhibitor, and immunoadjuvant resiquimod (R848; R) were synergistically encapsulated in solid lipid nanoparticles (SLNs). These SLNs demonstrated features of peptides targeting PD-L1, EGFR, and the endoplasmic reticulum, enclosed in a pH-responsive polyglutamic (PGA)-polyethylene glycol (PEG) shell. The homogeneous size and zeta potential of the nanoparticles were stable for 28 days at 4°C. The study substantiated the concurrent modulation of key pathways by the CB, miR, and R-loaded nanoformulation, prominently affecting VCP/Bip/ATF6, PD-L1/TGF-ß/IL-4, -8, -10, and TNF-α/IFN-γ/IL-1, -12/GM-CSF/CCL4 pathways. This adaptable nanoformulation induced durable antitumor immune responses and inhibited Panc-02 tumor growth by enhancing T cell infiltration, dendritic cell maturation, and suppressing Tregs and TAMs in mice bearing Panc-02 tumors. Furthermore, tissue distribution studies, biochemical assays, and histological examinations highlighted enhanced safety with PGA and peptide-modified nanoformulations for CB, miR, and/or R in Panc-02-bearing mice. This versatile nanoformulation allows tailored adjustment of the tumor microenvironment, thereby optimizing the localized delivery of combined therapy. These compelling findings advocate the potential development of a pH-sensitive, three-in-one PGA-PEG nanoformulation that combines a VCP inhibitor, a PD-L1 inhibitor, and an immunoadjuvant for cancer treatment via combinatorial chemo-immunotherapy.

Reliability and validity tests of the Chinese version of the Geriatric Locomotive Function Scale (GLFS-25) in tumor survivors.

Objective: To evaluate the reliability and validity of the Chinese-translated Geriatric Locomotive Function Scale (GLFS-25) for the assessment of locomotive syndrome (LS) in individuals surviving malignancies. Methods: 393 tumor survivors at a general hospital in China were recruited. The Chinese version of GLFS-25 was utilized to conduct a cross-sectional survey to ascertain the tool's efficacy in measuring LS in this cohort. The scale's validity was examined through content, structural and discriminant validity assessments, while its reliability was investigated by determining the internal consistency (via Cronbach's α coefficient) and test-retest reliability (via intragroup correlation coefficient, ICC). Results: The Chinese-adapted GLFS-25 demonstrated a robust scale-level content validity index of 0.94, while item-level content validity indices ranged from 0.83 to 1.00 across individual items. The suitability of the scale for structural validity assessment was confirmed via exploratory factor analysis, yielding a Kaiser-Meyer-Olkin measure of 0.930 and a significant Bartlett's test of sphericity (χ2 = 3217.714, df = 300, P < 0.001). Subsequent confirmatory factor analysis (CFA) extracted four distinct factors: Social Activity Engagement, Daily Living Ability, Pain Experience and Physical Mobility. These factors accounted for 72.668 % of the variance, indicating substantial construct validity for measuring LS among this population. CFA supported the model's fit with the following indices: χ2/df = 1.559, RMSEA = 0.077, GFI = 0.924, CFI = 0.941, NFI = 0.919, and TLI = 0.933. The factor loadings for the four factors ranged from 0.771 to 0.931, indicating the items corresponding to the four factors effectively represented the constructs they were designed to measure. The correlation coefficients among the four factors were between 0.306 and 0.469, all lower than the square roots of the respective AVEs (0.838-0.867). This suggests a moderate correlation among the four factors and a distinct differentiation between them, indicating the Chinese version of the GLFS-25 exhibits strong discriminant validity in Chinese tumor survivors. Reliability testing revealed a high Cronbach's α coefficient for the overall scale at 0.961, with the subscales yielding coefficients of 0.751, 0.836, 0.930, and 0.952. The overall ICC was determined to be 0.935, with subscale ICCs ranging from 0.857 to 0.941, reinforcing the scale's reliability in this context. Conclusions: The Chinese version of the GLFS-25 exhibits strong reliability and validity for the assessment of LS in tumor survivors. It may serve as a diagnostic tool for LS, contributing to the prevention and management of musculoskeletal disorders and enhancing the prognosis for this patient population.

Single-center retrospective study of the diagnostic value of double-balloon enteroscopy in Meckel's diverticulum with bleeding.

BACKGROUND: The study aimed to analyze the characteristic clinical manifestations of patients with intestinal disease Meckel's diverticulum (MD) complicated by digestive tract hemorrhage. Moreover, we aimed to evaluate the value of double-balloon enteroscopy (DBE) in MD diagnosis and the prognosis after laparoscopic diverticula resection. AIM: To evaluate the value of DBE in the diagnosis and the prognosis after laparoscopic diverticula resection for MD with bleeding. METHODS: The study retrospectively analyzed relevant data from 84 MD patients treated between January 2015 and March 2022 and recorded their clinical manifestations, auxiliary examination, and follow-up after laparoscopic resection of diverticula. RESULTS: (1) Among 84 MD patients complicated with hemorrhage, 77 were male, and 7 were female with an average age of 31.31 ± 10.75 years. The incidence was higher in men than in women of different ages; (2) Among the 84 MD patients, 65 (78.40%) had defecated dark red stools, and 50 (58.80%) had no accompanying symptoms during bleeding, indicating that most MD bleeding appeared a dark red stool without accompanying symptoms; (3) The shock index of 71 patients (85.20%) was < 1, suggesting that the blood loss of most MD patients was less than 20%-30%, and only a few patients had a blood loss of > 30%; (4) The DBE-positive rate was 100% (54/54), 99mTc-pertechnetate-positive scanning rate was 78% (35/45) compared with capsule endoscopy (36%) and small intestine computed tomography (19%). These results suggest that DBE and 99mTc-pertechnetate scans had significant advantages in diagnosing MD and bleeding, especially DBE was a highly precise examination method in MD diagnosis; (5) A total of 54 MD patients with hemorrhage underwent DBE examination before surgery. DBE endoscopy revealed many mucosal manifestations including normal appearance, inflammatory changes, ulcerative changes, diverticulum inversion, and nodular hyperplasia, with ulcerative changes being the most common (53.70%). This suggests that diverticular mucosal ulcer was the main cause of MD and bleeding; and (6) Laparoscopic dissection of diverticulae was performed in 76 patients, The patients who underwent postoperative follow-up did not experience any further bleeding. Additionally, follow-up examination of the 8 cases who had declined surgery revealed that 3 of them experienced a recurrence of digestive tract bleeding. These findings indicate that laparoscopic diverticula resection in MD patients complicated by bleeding had a favorable prognosis. CONCLUSION: Bleeding associated with MD was predominantly observed in male adolescents, particularly at a young age. DBE was a highly precise examination method in MD diagnosis. Laparoscopic diverticula resection effectively prevented MD bleeding and had a good prognosis.

Discovery of Novel Small-Molecule-Based Potential PD-L1/EGFR Dual Inhibitors with High Druggability for Glioblastoma Immunotherapy.

Based on the close relationship between programmed death protein ligand 1 (PD-L1) and epidermal growth factor receptor (EGFR) in glioblastoma (GBM), we designed and synthesized a series of small molecules as potential dual inhibitors of EGFR and PD-L1. Among them, compound EP26 exhibited the highest inhibitory activity against EGFR (IC50 = 37.5 nM) and PD-1/PD-L1 interaction (IC50 = 1.77 µM). In addition, EP26 displayed superior in vitro antiproliferative activities and in vitro immunomodulatory effects by promoting U87MG cell death in a U87MG/Jurkat cell coculture model. Furthermore, EP26 possessed favorable pharmacokinetic properties (F = 22%) and inhibited tumor growth (TGI = 92.0%) in a GBM mouse model more effectively than Gefitinib (77.2%) and NP19 (82.8%). Moreover, EP26 increased CD4+ cells and CD8+ cells in tumor microenvironment. Collectively, these results suggest that EP26 represents the first small-molecule-based PD-L1/EGFR dual inhibitor deserving further investigation as an immunomodulating agent for cancer treatment.

Pretransplant use of immune checkpoint inhibitors for hepatocellular carcinoma: A multicenter, retrospective cohort study.

Immune checkpoint inhibitors (ICIs) as a downstaging or bridging therapy for liver transplantation (LT) in hepatocellular carcinoma patients are rapidly increasing. However, the evidence about the feasibility and safety of pre-LT ICI therapy is limited and controversial. To this end, a multicenter, retrospective cohort study was conducted in 11 Chinese centers. The results showed that 83 recipients received pre-LT ICI therapy during the study period. The median post-LT follow-up was 8.1 (interquartile range 3.3-14.6) months. During the short follow-up, 23 (27.7%) recipients developed allograft rejection, and 7 of them (30.4%) were diagnosed by liver biopsy. Multivariate logistics regression analysis showed that the time interval between the last administration of ICI therapy and LT (TLAT) ≥ 30 days was an independent protective factor for allograft rejection (odds ratio = 0.096, 95% confidence interval 0.026-0.357; P < .001). Multivariate Cox analysis showed that allograft rejection was an independent risk factor for overall survival (hazard ratio = 9.960, 95% confidence interval 1.006-98.610; P = .043). We conclude that patients who receive a pre-LT ICI therapy with a TLAT shorter than 30 days have a much higher risk of allograft rejection than those with a TLAT longer than 30 days. The presence of rejection episodes might be associated with higher post-LT mortality.

Biomimetic MDSCs membrane coated black phosphorus nanosheets system for photothermal therapy/photodynamic therapy synergized chemotherapy of cancer.

Photothermal therapy is favored by cancer researchers due to its advantages such as controllable initiation, direct killing and immune promotion. However, the low enrichment efficiency of photosensitizer in tumor site and the limited effect of single use limits the further development of photothermal therapy. Herein, a photo-responsive multifunctional nanosystem was designed for cancer therapy, in which myeloid-derived suppressor cell (MDSC) membrane vesicle encapsulated decitabine-loaded black phosphorous (BP) nanosheets (BP@ Decitabine @MDSCs, named BDM). The BDM demonstrated excellent biosafety and biochemical characteristics, providing a suitable microenvironment for cancer cell killing. First, the BDM achieves the ability to be highly enriched at tumor sites by inheriting the ability of MDSCs to actively target tumor microenvironment. And then, BP nanosheets achieves hyperthermia and induces mitochondrial damage by its photothermal and photodynamic properties, which enhancing anti-tumor immunity mediated by immunogenic cell death (ICD). Meanwhile, intra-tumoral release of decitabine induced G2/M cell cycle arrest, further promoting tumor cell apoptosis. In vivo, the BMD showed significant inhibition of tumor growth with down-regulation of PCNA expression and increased expression of high mobility group B1 (HMGB1), calreticulin (CRT) and caspase 3. Flow cytometry revealed significantly decreased infiltration of MDSCs and M2-macrophages along with an increased proportion of CD4+, CD8+ T cells as well as CD103+ DCs, suggesting a potentiated anti-tumor immune response. In summary, BDM realizes photothermal therapy/photodynamic therapy synergized chemotherapy for cancer.

Broadening the Utility of Farnesyltransferase-Catalyzed Protein Labeling Using Norbornene-Tetrazine Click Chemistry.

Bioorthogonal chemistry has gained widespread use in the study of many biological systems of interest, including protein prenylation. Prenylation is a post-translational modification, in which one or two 15- or 20-carbon isoprenoid chains are transferred onto cysteine residues near the C-terminus of a target protein. The three main enzymes─protein farnesyltransferase (FTase), geranylgeranyl transferase I (GGTase I), and geranylgeranyl transferase II (GGTase II)─that catalyze this process have been shown to tolerate numerous structural modifications in the isoprenoid substrate. This feature has previously been exploited to transfer an array of farnesyl diphosphate analogues with a range of functionalities, including an alkyne-containing analogue for copper-catalyzed bioconjugation reactions. Reported here is the synthesis of an analogue of the isoprenoid substrate embedded with norbornene functionality (C10NorOPP) that can be used for an array of applications, ranging from metabolic labeling to selective protein modification. The probe was synthesized in seven steps with an overall yield of 7% and underwent an inverse electron demand Diels-Alder (IEDDA) reaction with tetrazine-containing tags, allowing for copper-free labeling of proteins. The use of C10NorOPP for the study of prenylation was explored in the metabolic labeling of prenylated proteins in HeLa, COS-7, and astrocyte cells. Furthermore, in HeLa cells, these modified prenylated proteins were identified and quantified using label-free quantification (LFQ) proteomics with 25 enriched prenylated proteins. Additionally, the unique chemistry of C10NorOPP was utilized for the construction of a multiprotein-polymer conjugate for the targeted labeling of cancer cells. That construct was prepared using a combination of norbornene-tetrazine conjugation and azide-alkyne cycloaddition, highlighting the utility of the additional degree of orthogonality for the facile assembly of new protein conjugates with novel structures and functions.

Isopropanol-promoted DNA extraction by polydopamine functionalized magnetic particles based on metal coordination.

High-quality DNA is an important guarantee to start downstream experiments in many biological and medical research areas. Magnetic particle-based DNA extraction methods from blood mainly depend on electrostatic adsorption in a low-pH environment. However, the strong acidic environment can influence the DNA stability. Herein, a polydopamine-functionalized magnetic particle (PDA@Fe3O4)-based protocol was developed for DNA extraction from whole blood samples. In the protocol, Mg2+ and Ca2+ were utilized to bridge the adsorption of DNA by PDA@Fe3O4 via the metal-mediated coordination. Isopropanol was found to efficiently promote DNA adsorption by triggering the change of the conformation of DNA from B-form to more compact A-form. In 50 % isopropanol solution, the DNA adsorption efficiency was nearly 100 % in the presence of 0.5 mM Ca2+ or 1.5 mM Mg2+. The role of metal ions and isopropanol in DNA adsorption was explored. The protocol averts the strong acidic environment and PCR inhibitors, such as high concentrations of salt or polyethylene glycol. It demonstrates superiority in DNA yield (59.13 ± 3.63 ng µL-1) over the commercial kit (27.33 ± 4.98 ng µL-1) and phenol-chloroform methods (37.90 ± 0.47 ng µL-1). In addition, to simplify the operastion, an automated nucleic acid extraction device was designed and fabricated to extract whole genomic DNA from blood. The feasibility of the device was verified by extracting DNA from cattle and pig blood samples. The extracted DNA was successfully applied to discriminate the beef authenticity by a duplex PCR system. The results demonstrate that the DNA extraction protocol and the automated device have great potential in blood samples.

Therapeutic and fluorescence evaluation of 20% 5-aminolevulinic acid-mediated photodynamic therapy in actinic keratosis.

BACKGROUND: Actinic keratosis (AK) is a precancerous lesion that occurs in areas that are chronically exposed to sunlight and has the potential to develop into invasive cutaneous squamous cell carcinoma (cSCC). We investigated the efficacy of 20% 5-aminolevulinic acid-photodynamic therapy (ALA-PDT) with LED red light for the treatment of AK in Chinese patients by examining changes in dermoscopic features, histopathology and fluorescence after treatment. METHODS: Twenty-eight patients with fourty-six AK lesions from March 2022 to September 2023 were treated with 20% ALA, and 3 hours later, they were irradiated with LED red light (80-100 mW/cm2) for 20 minutes. A session of 20% ALA-PDT was performed once a week for three consecutive weeks, and the dermoscopic, histopathological, fluorescent and photoaging outcomes were measured one week after the treatment. RESULTS: One week after ALA-PDT, complete remission (CR) was reached in 53.6% of patients. The CR of Grade I AK lesions was 100%, that of Grade II lesions was 71.4%, and that of Grade III lesions was 38.1%. There was a significant improvement in the dermoscopic features, epidermal thickness and fluorescence of the AK lesions. The presence of red fluorescence decreased, and there was an association between CR and post-PDT fluorescence intensity. ALA-PDT also exhibited efficacy in treating photoaging, including fine lines, sallowness, mottled pigmentation, erythema, and telangiectasias, and improved the global score for photoaging. There were no serious adverse effects during or after ALA-PDT, and 82.1% of the patients were satisfied with the treatment. CONCLUSION: AK lesions can be safely and effectively treated with 20% ALA-PDT with LED red light, which also alleviates photoaging in Chinese patients, including those with multiple AKs. This study highlights the possibility that fluorescence could be used to diagnose AK with peripheral field cancerization and evaluate the efficacy of ALA-PDT.

The prognostic nutritional index as a predictor of efficacy and early recurrence for adjuvant transarterial chemoembolization in hepatocellular carcinoma.

BACKGROUND AND AIMS: Postoperative adjuvant transcatheter arterial chemoembolization (TACE) can prevent recurrence of hepatocellular carcinoma (HCC) in certain patients. This study aimed to identify the potential beneficiaries of adjuvant TACE. METHODS: 477 patients who underwent curative resection for HCC were enrolled in this retrospectively cohort study. The trajectory of the prognostic nutritional index (PNI) during the perioperative period was fitted using a latent-class growth mixed model. The association between adjuvant TACE and recurrence-free survival in each PNI group was assessed using the Kaplan-Meier curve. Furthermore, Cox regression analysis was conducted to identify the risk factors for early recurrence after adjuvant TACE and develop a nomogram model. RESULTS: Patients in the PNI group III had a high risk of recurrence and could benefit from adjuvant TACE (P = 0.009). The prognostic prediction model for adjuvant TACE (PAT) incorporated eight variables (PNI, tumor size, tumor number, microvascular invasion, sex, aspartate aminotransferase, gamma-glutamyl transferase, and degree of differentiation). Patients with PAT score >330 and 235-330 had significantly higher recurrence rates than those with PAT score <235 (P < 0.001). CONCLUSION: PNI may help guide the selection of adjuvant TACE beneficiaries. PAT demonstrated a high accuracy in predicting the prognosis of patients who underwent postoperative TACE.

Identification of an immune-related signature as a prognostic classifier for patients with early-stage head and neck squamous cell carcinoma.

Background: Head and neck squamous cell carcinoma (HNSCC) is the most common type and accounts for 90% of all head and neck cancer cases. Despite advances in early diagnosis and treatment strategies-chemotherapy, surgical resection, and radiotherapy-5-year survival remains grim. For patients with early-stage HNSCC, accurately predicting clinical outcomes is challenging. Considering the pivotal role of the immune system in HNSCC, we developed a reliable immune-related gene signature (IRGS) and explored its predictive accuracy in patients with early-stage HNSCC. Methods: We examined immune gene expression profiles and clinical information from 230 early-stage HNSCC specimens, including 100 cases from The Cancer Genome Atlas (TCGA), 49 cases from the Gene Expression Omnibus (GEO; GSE65858), and 81 cases from an independent clinical cohort. The prognostic signature was constructed using Kaplan-Meier analysis and the least absolute shrinkage and selection operator (LASSO) Cox algorithm. We also explored the IRGS-related biological pathways and immune landscape using bioinformatics analysis. Results: A nine-immune-gene signature was generated to significantly stratify patients into high and low-risk groups. High risk patients exhibited shorter survival time [hazard ratio (HR) =13.795, 95% confidence interval (CI): 3.275-58.109, P<0.001]. The signature demonstrated robust prognostic ability in the training and validation sets and could independently predict overall survival (OS) and relapse-free survival (RFS). Subsequently, the receiver operating characteristic (ROC) curve and C-index confirmed the signature's predictive accuracy compared to clinical parameters. Additionally, cases classified as low risk showed more immune cell infiltration than high-risk cases. Conclusions: Our novel IRGS is a reliable and robust classifier for accurate patient stratification and prognostic evaluation. Future studies will attempt to affirm the signature's clinical application to early-stage HNSCC.

Discovery of 4-phenyl-1H-indazole derivatives as novel small-molecule inhibitors targeting the PD-1/PD-L1 interaction.

The inhibition of the programmed cell death-1 (PD-1)/programmed cell death-ligand 1 (PD-L1) pathway with small molecules is a promising approach for cancer immunotherapy. Herein, novel small molecules compounds bearing various scaffolds including thiophene, thiazole, tetrahydroquinoline, benzimidazole and indazole were designed, synthesized and evaluated for their inhibitory activity against the PD-1/PD-L1 interaction. Among them, compound Z13 exhibited the most potent activity with IC50 of 189.6 nM in the homogeneous time-resolved fluorescence (HTRF) binding assay. Surface plasmon resonance (SPR) assay demonstrated that Z13 bound to PD-L1 with high affinity (KD values of 231 nM and 311 nM for hPD-L1 and mPD-L1, respectively). In the HepG2/Jurkat T co-culture cell model, Z13 decreased the viability rate of HepG2 cells in a concentration-dependent manner. In addition, Z13 showed significant in vivo antitumor efficacy (TGI = 52.6 % at 40 mg/kg) without obvious toxicity in the B16-F10 melanoma model. Furthermore, flow cytometry analysis demonstrated that Z13 inhibited tumor growth in vivo by activating the tumor immune microenvironment. These findings indicate that Z13 is a promising PD-1/PD-L1 inhibitor deserving further investigation.

Glucose metabolism reprogramming in gynecologic malignant tumors.

The incidence and mortality of gynecological tumors are progressively increasing due to factors such as obesity, viral infection, unhealthy habits, as well as social and economic pressures. Consequently, it has emerged as a significant threat to women's health. Numerous studies have revealed the remarkable metabolic activity of tumor cells in glycolysis and its ability to influence malignant biological behavior through specific mechanisms. Therefore, it is crucial for patients and gynecologists to comprehend the role of glycolytic proteins, regulatory molecules, and signaling pathways in tumorigenesis, progression, and treatment. This article aims to review the correlation between abnormal glucose metabolism and gynecologic tumors including cervical cancer (CC), endometrial carcinoma (EC), and ovarian cancer (OC). The findings from this research will provide valuable scientific insights for early screening, timely diagnosis and treatment interventions while also aiding in the prevention of recurrence among individuals with gynecological tumors.

Efficacy of metastatic lesion radiotherapy in patients with metastatic nasopharyngeal carcinoma: A multicenter retrospective study.

OBJECTIVE: We investigated the efficacy of metastatic lesion radiotherapy (MLRT) in patients with metastatic nasopharyngeal carcinoma (mNPC). MATERIALS AND METHODS: Patients with mNPC from three institutions were included in this study. Propensity score matching (PSM) was employed to ensure comparability between patient groups. Overall survival (OS) rates were assessed using the Kaplan-Meier method and compared using the log-rank test. Prognostic factors were identified using univariate and multivariate Cox hazard analyses. Subgroup analyses were conducted to assess the effects of MLRT on specific patient populations. RESULTS: We analyzed data from 1157 patients with mNPC. Patients who received MLRT had significantly better OS than those who did not, both in the original (28 vs. 21 months) and PSM cohorts (26 vs. 23 months). MLRT was identified as an independent favorable predictor of OS in multivariate analyses, with hazard ratios of 0.67. The subgroup analysis results indicated that radiotherapy effectively treated liver, lung, and bone metastatic lesions, particularly in patients with a limited tumor burden. Higher total radiation doses of MLRT (biologically effective dose (BED) ≥ 56 Gy) were associated with improved OS, while neither radiation technique nor dose fractionation independently influenced prognosis. CONCLUSIONS: MLRT offers survival advantages to patients diagnosed with mNPC. Patients with limited metastatic burden derive the most benefit from MLRT, and the recommended regimen for MLRT is a minimum BED of 56 Gy for optimal outcomes.