Abstract Abstract photothermal therapy (PTT) usually results in the increase of heat shock proteins (HSPs), which leads to side effects and low efficiency. Protein degradation-targeting chimeras (PROTAC) provides a chance to degrade the HSPs, but the smart PROTAC during PTT is still scarce. Here, we designed and constructed a PROTAC-loaded peptide nanoparticle (PJS) for near-infrared II (NIR-II) fluorescence imaging-guided and mild tumor photothermal/photodynamic synergistic therapy. The nanoparticles self-assembled from acid-sensitive amphiphilic polypeptides, encapsulating both the photodynamic/photothermal dual-effect photosensitizer TPBr-Cy and the PROTAC molecules targeting heat shock protein 90 (HSP90) degradation. PJS exhibited good biocompatibility and responsiveness to the acidic tumor microenvironment. Upon accumulation at tumor sites and responsive release, the enhanced fluorescence signal of TPBr-Cy enabled high-resolution NIR-II fluorescence imaging, providing navigation for precision therapy. Under single near-infrared laser irradiation, PJS simultaneously generated reactive oxygen species (ROS) for PDT effects while effectively maintaining local temperatures within the mild photothermal range (∼45 °C), minimizing the thermal damage to surrounding normal tissues. Crucially, the released PROTAC molecules specifically degraded HSP90 protein, effectively disrupting tumor cells’ heat defense mechanisms under mild thermal stress and significantly enhancing sensitivity to mild photothermal therapy. This intelligent responsive peptide nanoplatform, integrating NIR-II imaging, PROTAC-mediated protein degradation, PDT, and mPTT, demonstrated promising synergistic antitumor effects.

Objective Minimally invasive liver resection (MILR) is a common surgical treatment for hepatocellular carcinoma (HCC). However, the current difficulty scoring system for MILR is limited to small samples or a single center, and a scoring system to assess surgery only for HCC is rare. Thus, we developed and validated a novel difficulty prediction system based on data from multiple centers to assess the surgical difficulty of MILR for treating HCC. Methods This retrospective multicenter cohort study included patients who underwent MILR for resectable HCC between June 2011 and November 2022 at eight minimally invasive surgical centers in China. The cohort was randomly divided into a training dataset and a validation dataset at a 3:1 ratio. Univerable and multivariable logistic regression analyses were performed on the training dataset to identify independent risk factors for surgical difficulty and construct a prediction model. The performance of the model was validated by the validation dataset, and its discriminative ability, calibration, and clinical effectiveness were assessed using receiver operating characteristic curves and decision curve analysis. Results This study included 776 patients, with 582 patients in the training cohort and 194 patients in the validation cohort. Cirrhosis (OR, 1.91; 95% CI, 1.12–2.64), maximum tumor diameter (OR, 1.4; 95% CI, 1.26–1.56), and surgical resection extent (grade B: OR, 11.92; 95% CI, 3.53–38.32; grade C: OR, 46.97; 95% CI, 9.31–228.18; grade D: OR, 32.85; 95% CI, 9.25–111.29) were identified as independent risk factors influencing the challenge of MILR for HCC. The AUC was 0.783 (95% CI, 0.746–0.820) for the training cohort and 0.717 (95% CI, 0.643–0.791) for the validation cohort. Decision curve analysis revealed that this clinical model has strong practicality. Conclusions This novel nomogram performed well in predicting the difficulty of MILR in treating HCC on the basis of Eastern data.

Background:Pancreatic adenocarcinoma (PAAD) is highly aggressive, and its tumor microenvironment has significant metabolic and immune microenvironment complexity and genomic instability. In this study, by integrating the metabolic pathway activity score and clinical data, we constructed a novel risk assessment model to reveal the unique biological behavior and clinical significance behind different PAAD subtypes. Methods:In this study, the transcriptome and clinical data of TCGA and GSE57495 databases were integrated to explore the interaction between metabolic pathways. Based on unsupervised clustering analysis of pathway activity and survival prognosis, patients with PAAD were classified into metabolic subtypes with significant prognostic differences. Subsequently, we assessed the heterogeneity of these subtypes in terms of clinical outcomes, genomic characteristics, and immune microenvironment composition. Based on the differentially expressed genes (DEGs) among metabolic subtypes, a clinical prognostic risk model and nomogram were constructed, which were double-validated by GSE57495-independent cohort and GSE57495 + TCGA-PAAD combined cohort. Finally, the correlations between risk scores (RSs) and signaling pathway activity and tumor immune microenvironment characteristics were evaluated. Results:Based on metabolic pathway correlation and prognostic information, 240 patients in the TCGA-PAAD and GSE57495 datasets were divided into three subgroups. There were significant differences between subgroups in gene expression, pathway activity, clinical prognosis, and immune infiltration characteristics among the subtypes. Using machine learning algorithms, an RS model was constructed from DEGs among the subgroups, with the random forest method showing the best performance. A nomogram integrating the RS and clinical indicators demonstrated excellent predictive accuracy for 1-, 3-, and 5-year survival rates, confirming the RS as an independent prognostic factor. High- and low-risk groups exhibited significant differences in immune infiltration, pathway activity, and gene mutations. Drug sensitivity analysis showed that the high-risk group was more sensitive to AZD6244, ABT737, and other drugs. Conclusion:This study stratified patients with PAAD into three subgroups based on metabolic pathways and prognostic information, revealing significant differences in clinical outcomes, immune characteristics, and genetic mutations. The robust RS model developed from these findings demonstrated strong predictive power for patient survival and identified promising therapeutic strategies, providing valuable insights for advancing precision medicine in PAAD.

BACKGROUND & AIMS:Liver regeneration is a tightly regulated process requiring coordinated interactions between hepatocytes and non-parenchymal cells; however, its molecular mechanisms remain incompletely defined. Here, we aimed to investigate the role of interferon-related developmental regulator 1 (IFRD1) in regulating metabolic-immune crosstalk during liver regeneration. METHODS:We integrated public transcriptomic datasets, human liver disease samples, and multiple in-house-generated experimental models to characterize the dynamic expression of IFRD1 during liver regeneration. Genetic loss-of-function approaches, including global and cell type-specific knockout mice, together with adeno-associated virus-mediated gain-of-function strategies, were combined with single-nucleus RNA-seq, ATAC-seq, metabolic and biochemical assays, protein interaction analyses, and in vivo rescue experiments. RESULTS:Hepatocyte IFRD1 was rapidly induced during the early phase of liver regeneration in mice but markedly diminished in human chronic liver disease. Hepatocyte-specific loss of IFRD1 impaired liver repair and regeneration, whereas IFRD1 overexpression enhanced regenerative responses across multiple models, including partial hepatectomy, toxic liver injury, and hepatic ischemia-reperfusion injury. Mechanistically, IFRD1 was required to sustain hepatocyte β-oxidation and mitochondrial ATP production by stabilizing SLC25A5 through competition with the E3 ubiquitin ligase TRIM21. This ATP boost enables chromatin remodeling in hepatocytes, promoting CCL/CXC chemokine expression to recruit CCR2+ monocytes and expand the regenerative GPNMB+ macrophage pool. Notably, IFRD1 overexpression restored liver regenerative capacity after partial hepatectomy in mice with metabolic dysfunction-associated steatohepatitis or diethylnitrosamine-induced liver fibrosis. CONCLUSIONS:Our findings define IFRD1 as a key immunometabolic regulator of liver regeneration, linking hepatocyte metabolic control to macrophage-driven regenerative responses. These results support the therapeutic potential of targeting IFRD1 to enhance regenerative capacity in liver disease. IMPACT AND IMPLICATIONS:Liver regeneration is essential for recovery from surgical resection and acute injury, yet therapeutic options to enhance this process remain limited. Our study identifies the IFRD1-SLC25A5-ATP axis as a critical regulator that links hepatocyte energy metabolism with the expansion of a pro-regenerative macrophage pool. This previously unrecognized regulatory node provides a scientific rationale for developing therapeutic strategies that enhance IFRD1 function to accelerate liver repair. While upstream regulators of IFRD1 remain undefined, these findings lay a foundation for improving regenerative outcomes in patients with compromised liver function.

Background:While curative-intent resection for gallbladder cancer (GBC) is being increasingly performed in elderly patients, perioperative morbidity and long-term oncological outcomes in this population remain unclear. Methods:Consecutive patients with GBC who underwent curative-intent resection (2016-2020) were identified from a multicentre database and stratified as elderly (>70 years) or younger (≤70 years). Propensity score matching (PSM) and inverse probability of treatment weighting (IPTW) were used to minimise selection bias. The outcomes compared included overall survival (OS), cancer-specific survival (CSS) and short-term outcomes. Logistic regression was used to identify risk factors for major morbidity and Cox regression was used for CSS, with the Fine-Gray competing risk model further applied to account for non-cancer-related death in the analysis of CSS. Results:Among the 575 patients enrolled, 432 were younger and 143 were elderly. After 1:1 PSM and IPTW, elderly patients had significantly higher 90-day major morbidity rates than younger patients (p=0.029 and p=0.010, respectively), but also demonstrated better CSS in both cohorts (p=0.038 and p<0.001, respectively). OS was significantly longer in elderly patients only after PSM (p<0.001), with no significant difference after IPTW (p=0.684). Multi-adjusted analysis confirmed that advanced age was an independent risk factor for major morbidities (original cohort: OR 1.71 (95% CI 1.12 to 2.59); PSM: OR 1.88 (95% CI 1.08 to 3.30); IPTW: OR 1.83 (95% CI 1.17 to 2.82)) but was associated with longer CSS (original cohort: HR 0.65 (95% CI 0.44 to 0.97); PSM: HR 0.29 (95% CI 0.18 to 0.45); IPTW: HR 0.62 (95% CI 0.42 to 0.90); Fine-Gray model: HR 0.34 (95% CI 0.30 to 0.39)). Conclusion:Despite a higher risk of major postoperative morbidity, advanced age itself might not be considered a contraindication for curative-intent resection. Selected elderly patients with GBC may achieve superior CSS compared to their younger counterparts.

Accurate identification of tumor margins during liver cancer resection is crucial for improving prognosis and reducing postoperative complications. This study investigated the feasibility of using a galactose-targeted nanofluorescent probe known as Gal-OH-BDP NPs (GOB NPs), which emits in the NIR-II window, for fluorescence imaging of orthotopic hepatocellular carcinoma in animal models. In vitro imaging was performed with Intralipid emulsion and chicken breast to assess the tissue penetration depth of the GOB NPs and ICG in the NIR window. In vivo NIR-I/II imaging was conducted in orthotopic liver tumor animal models. Pathological validation confirmed that intratumoral injection of GOB NPs resulted in targeted accumulation within liver cancer tissue. Quantitative image analysis revealed that GOB NPs-mediated NIR-II imaging exhibited the highest fluorescence intensity at the tumor site and the lowest background fluorescence in the liver, thus resulting in the highest tumor-to-normal liver tissue ratio (TNR) and the highest tumor margin resolution. Additionally, GOB NPs-mediated NIR-II imaging maintained effective tumor margin visibility at a depth of 8 mm, whereas ICG-mediated NIR-I/II imaging demonstrated effective detection depths limited to 2 and 5 mm, respectively. Following intravenous injection, the GOB NPs exhibited negative staining, thus clearly delineating the tumor boundaries and achieving a high contrast between the tumor and liver tissues.

Purpose:A plethora of studies have demonstrated an association between preoperative inflammatory immunonutritional status and the prognosis of patients with hepatocellular carcinoma. Nonetheless, there is a paucity of research examining the predictive value of inflammatory immunonutritional indicators for postoperative liver failure in this patient population. This study seeks to identify independent predictors of post hepatectomy liver failure (PHLF) in patients with hepatocellular carcinoma and to develop a nomogram model. Patients and Methods:Clinical data were collected from 760 patients diagnosed with hepatocellular carcinoma who underwent surgical treatment at a hospital in China between January 2020 and January 2024. The dataset was randomly divided into a training set (n=570, 75%) and a validation set (n=190, 25%). To identify independent predictors of PHLF in these patients, univariate analysis and least absolute shrinkage and selection operator (LASSO) regression were employed. Subsequently, a multivariate logistic regression model was developed to construct a predictive model. The predictive performance of the nomogram was evaluated using receiver operating characteristic (ROC) curve analysis, calibration curve assessment, and decision curve analysis (DCA). Results:AAPR, ALBI, GAR, LMR, PNI, INR, APTT, and TT are independent factors associated with PHLF in patients with hepatocellular carcinoma. The C indices for the training and validation datasets were 0.691 (95% CI: 0.634-0.747) and 0.680 (95% CI: 0.556-0.804), respectively. The area under the curve (AUC) and calibration curve analyses demonstrated the nomogram's accuracy in predicting PHLF in this patient population. Furthermore, DCA indicated that the model provides a significant clinical net benefit. A comparison was made of the predictive efficacy of the nomogram prediction model and the associated composite liver function score. ROC curves were plotted for the nomogram prediction model, Child-Pugh score and ALBI score, and AUC values were calculated, which were 0.686 (95% CI 0.635-0.737) for the prediction model, 0.558(95% CI 0.512-0.603) for the Child-Pugh score. The AUC for ALBI score was 0.577 (95% CI 0.530-0.624), indicating that this nomogram prediction model was more effective than other scoring systems in predicting the study population in our center. In this study population, the nomogram model demonstrated an AUC of 0.707 (95% CI 0.620-0.794) for Child-Pugh score grade A and 0.572 (95% CI 0.501-0.643) for Child-Pugh score grade B. For tumors with a diameter of less than 5 cm, the AUC was 0.679 (95% CI 0.608-0.749), and for patients with tumors with a diameter of at least 5 cm, the AUC was 0.715 (95% CI 0.643-0.787). Conclusion:We have developed an innovative nomogram model designed to predict the incidence of PHLF in patients diagnosed with hepatocellular carcinoma. This nomogram has a good predictive value for PHLF in HCC patients and is important for clinicians to manage patients after hepatectomy.

Photothermal therapy (PTT) utilizes localized hyperthermia above 50 °C generated by nanomaterials upon exposure to near-infrared (NIR) laser light for effective cancer cell eradication. Yet, in high-temperature PTT, tumor cells develop heat stress tolerance due to elevated heat shock protein (HSP) levels, diminishing therapeutic efficacy. Moreover, excessive heat can trigger inflammatory conditions and promote cancer metastasis. Targeting the glycolytic pathway in highly metabolically active tumor cells offers a promising strategy for inducing starvation therapy, capitalizing on their vigorous energy demands amidst rapid proliferation. Here, we synthesized a highly luminous NIR-II dye, FNF, followed by its encapsulation alongside myricetin (My) within amphiphilic polypeptide carriers through a self-assembly method. The resulting nanoparticles exhibited great NIR-II imaging capabilities and boasted a notable photothermal conversion efficiency of 55.58 %. Furthermore, My effectively impeded glucose transport facilitated by glucose transporter protein 1 (GLUT1), curtailing glucose supply to tumor cells. This interference disrupted mitochondrial energy production, resulting in decreased adenosine triphosphate (ATP) synthesis and subsequent downregulation of HSP70 expression. By leveraging this approach, which targeted HSP expression via GLUT1 inhibition, we enhance the efficacy of PTT while achieving a synergistic effect for mild photothermal therapy through starvation. STATEMENT OF SIGNIFICANCE: High expression of heat shock proteins (HSPs) in cancer cells impairs the efficacy of photothermal therapy (PTT) and triggers inflammation or metastasis, among other effects. Rapid malignant proliferation of tumor cells results in high energy metabolism, so interfering with their glucose metabolism to inhibit the glycolytic process is a feasible route for tumor starvation therapy. Here, we employed an amphiphilic polypeptide encapsulated photosensitizer (FNF) and myricetin (My) to construct nanoparticles with both NIR-II imaging capability and high photothermal conversion efficiency (55.58 %). Among them, My blocked glucose transport mediated by glucose transporter protein 1 (GLUT1), reduced the glucose supply and ATP synthesis in cancer cells, and then down regulated HSP70 expression. Thus, this strategy achieves starvation synergistic mild photothermal therapy through metabolic disruption.

Introduction: Laennec’s capsule serves as a critical anatomical landmark in liver resection. Despite its potential, a lack of large-scale prospective studies limits the widespread use of the Laennec approach for minimally invasive hepatectomy. This multicenter cohort study aimed to compare the outcomes of the traditional and Laennec approaches in minimally invasive anatomical hepatectomy across multiple centers in China. Methods: A total of 445 patients from 11 centers were included, with 339 undergoing the Laennec approach and 106 receiving the traditional approach. Intraoperative parameters such as the duration of hepatic pedicle isolation, hepatic vein exposure, parenchymal transection, and liver mobilization were analyzed. Postoperative outcomes, including recurrence-free survival and R0 resection rates, were also assessed. Additionally, a series of subgroup analyses were conducted to evaluate the efficacy of the Laennec approach. Results: The Laennec approach demonstrated notable intraoperative advantages, including reduced durations for hepatic pedicle isolation, liver mobilization, hepatic vein exposure, and parenchymal transection. Robotic-assisted procedures, in particular, showed superior outcomes when compared with laparoscopic platform. The Laennec approach proved highly effective across various liver diseases, particularly hepatocellular carcinoma, hemangioma, and hepatolithiasis. The Laennec gap, a distinct gap between the liver parenchyma and surrounding vasculature, played a key role in identifying candidates for the Laennec approach. Subgroup analysis revealed that although the Laennec approach provides significant intraoperative benefits, these advantages do not seem not to translate into substantial postoperative improvements. Conclusions: The Laennec approach offers clear intraoperative advantages over the traditional approach when utilizing laparoscopic or robotic systems. These findings support the Laennec approach as a standardized technique for anatomical liver resection.

Purpose:Liver venous deprivation (LVD; simultaneous portal vein embolization and hepatic vein embolization) has been the latest surgical strategy for rapid future liver remnant (FLR) hypertrophy. The aim of this study was to assess the feasibility, safety, and efficacy of simultaneous LVD following hepatic arterial chemoembolization (TACE-LVD) before major hepatectomy for hepatocellular carcinoma (HCC). Patients and Methods:A retrospective analysis of the outcomes of 23 HCC patients who underwent TACE-LVD at our center between October 2019 and October 2023 was conducted. An assessment of postoperative complications, FLR volume, liver function, and tumor response was performed. Results:All patients successfully underwent TACE-LVD. No other serious complications occurred except in 1 patient who underwent puncture drainage due to excessive pleural effusion. Following TACE-LVD, transaminase levels peak two days before rapidly decreasing and return to preoperative levels within one week. The ratio of FLR to standardized liver volume increased from 35.9% (interquartile range [IQR], 8.6) to 46.4% (IQR, 8.2), with a mean degree of hypertrophy and kinetic growth rate of 13.2% (IQR, 5.4) and 4.4% (IQR, 1.8) per week, respectively. At the first assessment after TACE-LVD, most patients exhibited sufficient FLR for hepatectomy, except for 4 patients with cirrhosis. The modified response evaluation criteria for solid tumor assessment revealed a disease control rate of 95.7%, with only 1 patient (Barcelona Clinic Liver Cancer stage C) developing intrahepatic disease progression. Conclusion:TACE-LVD seems to be a feasible, safe, and effective strategy for rapid FLR hypertrophy. Moreover, TACE-LVD may be a therapeutic choice if insufficient FLR hypertrophy precludes resection. This strategy warrants further exploration.

Stable organic radicals have emerged as promising candidates in biotheranostics owing to their unique electronic configurations and tunable photophysical characteristics. Among these, dicyanomethyl radical derivatives stand out as key players in dynamic covalent chemistry, demonstrating exceptional temperature-responsive reversible polymerization-dissociation dynamics and remarkable long-wavelength absorption profiles despite their low molecular weights. In this work, we developed a novel radical system designated CNPJ through the strategic incorporation of julolidine into a dicyanomethyl-functionalized phenoxazine scaffold. The stability and radical nature of CNPJ were first corroborated by nucleus-independent chemical shift (NICS) calculations. Structural analyses revealed two critical phenomena enabled by efficient spin delocalization and intermolecular charge transfer: i) polarity-triggered radical center redistribution and ii) thermally regulated monomer‒π dimer equilibrium. These distinctive features confer enhanced structural rigidity and an exceptional absolute photoluminescence quantum yield of 2.57%, a remarkably high value for near-infrared emitters, accompanied by a bathochromically shifted π dimer absorption band centered at 960 nm. Capitalizing on these attributes, we engineered a theranostic platform by integrating CNPJ with the pH-responsive amphiphilic polymer PEA through pifithrin-μ (PES) inhibitor mediation. This system achieves ultrahigh-brightness fluorescence imaging-guided mild photothermal tumor therapy, yielding promising therapeutic outcomes.

Objective: Patients with hepatocellular carcinoma (HCC) who undergo curative hepatectomy may experience varying remnant liver volumes. Our study aimed to evaluate whether the extent of liver resection has an effect on postoperative recurrence in HCC patients at China Liver Cancer Staging (CNLC) Ib stage. Methods: A retrospective analysis was conducted on 197 patients who underwent hepatectomy for a solitary HCC lesion measuring >= 5 cm (CNLC Iota b stage) between January 2019 and June 2022. Patients were divided into a major hepatectomy (MAH) group (n=70) and a minor hepatectomy (MIH) group (n=127) based on the extent of liver resection. Recurrence-free survival (RFS) was compared between the two groups. Propensity score matching (PSM) was employed to minimize bias in the retrospective analysis. Results: Patients who underwent MAH had a greater total complication rate than those who underwent MIH (35.7 vs. 11.8%, P<0.001). The median RFS was 14.6 months (95% CI: 11.1-18.1) for the MAH group and 24.1 months (95% CI: 21.2-27.1) for the MIH group (P<0.001). After PSM, patients who underwent MAH still had a greater total complication rate than those who underwent MIH (36.7 vs. 16.3%, P=0.037). The median RFS was 13.2 months (95% CI: 15.1-21.7) for the MAH group and 22.3 months (95% CI: 18.1-26.5) for the MIH group (P=0.0013). The Cox regression model identified MAH as an independent poor predictor for HCC recurrence (hazard ratios of 1.826 and 2.062 before and after PSM, respectively; both P<0.05). Conclusion: MIH can be performed with fewer postoperative complications and contributes to improved RFS in patients with HCC at CNLC Iota b stage compared to MAH. Parenchyma-sparing resection should be considered the first choice for these HCCs.

INTRODUCTION:This study investigated the relationship between textbook outcomes of liver surgery (TOLS) and overall survival (OS) in patients who underwent curative-intent resection of GBC. METHODS:Patients with GBC who underwent curative-intent resection between 2014 and 2021 were selected from 16 hospitals. Patients were divided into either the TOLS group or the non-TOLS group, according to whether TOLS were observed. Patients who died within 90 days of surgery were excluded prior to the survival analysis. Log-rank test was used to compare the difference in the OS rate between TOLS and non-TOLS groups. Univariate and multivariate analyses were performed using Cox regression analysis to identify factors independently associated with OS. RESULTS:A total of 913 patients were selected, 565 (61.9%) exhibited TOLS. The 5-year OS rate in the TOLS group was significantly higher than that in the non-TOLS group (45.4% vs. 21.9%; p < 0.001). Multivariate Cox regression analysis confirmed TOLS, total bilirubin level >54 µmol/mL, carcinoembryonic antigen level >5 µg/mL, CA 19-9 level >37 U/L, poor differentiation, stages T2 and T3/4 according to the 8th edition AJCC T staging manual, N1 and N2 according to the 8th edition AJCC N staging manual, and adjuvant chemotherapy as independent risk factors that affect OS after curative-intent resection of GBC. CONCLUSION:Among patients who undergo curative-intent resection of GBC, approximately 61.9% experience TOLS. TOLS are not only the optimal short-term outcome but also associated with long-term survival.

The commonly employed strategies for engineering second near-infrared (NIR-II) organic phototheranostic agents are based on expanding conjugated backbone length, strengthening donor (D)-acceptor (A) effect, or forming J-aggregates. We constructed the D-A-D' structure by incorporating strong electron-donating methoxy and tetraphenylethene (TPE) moieties on the electron-deficient Aza-BODIPY core, and simultaneously expanded the π-conjugation effect by introducing thiophene groups, to obtain a dye BDP-TPE. Next, the nanoparticles P-TPE were prepared via the assembly of BDP-TPE with amphiphilic polypeptides (mPEG2000-P(Asp)10), and successfully constructed the J-aggregates. The obtained P-TPE exhibited strong absorption and fluorescence with maxima at 808 and 1018 nm, respectively, with a conspicuous absolute quantum yield of 0.241 %. Moreover, P-TPE also showed excellent biocompatibility, and high photothermal conversion efficiency of 61.15 %, and excellent resistance to pH, long-term storage, and photobleaching. In vitro and in vivo experiments revealed that P-TPE exhibited good biocompatibility and effectively achieved NIR-II fluorescence imaging-guided PTT with complete tumor ablation under 808 nm laser irradiation. These results provided good evidence for the use of P-TPE as a NIR-II fluorescence imaging-guided PTT therapeutic agent in vivo.

Correction for 'In situ formation of J-aggregate in the tumor microenvironment using acidity responsive polypeptide nanoparticle encapsulating galactose-conjugated BODIPY dye for NIR-II phototheranostics' by Huiping Dang et al., J. Mater. Chem. B, 2022, 10, 5279-5290, https://doi.org/10.1039/D2TB00705C.

Glutamine addiction represents a metabolic vulnerability of cancer cells; however, effective therapeutic targeting of the pathways involved remains to be realized. Here, we disclose the critical role of interferon-related developmental regulator 1 (IFRD1) in the adaptive survival of hepatocellular carcinoma (HCC) cells during glutamine starvation. IFRD1 is induced under glutamine starvation to inhibit autophagy by promoting the proteasomal degradation of the key autophagy regulator ATG14 in a TRIM21-dependent manner. Conversely, targeting IFRD1 in the glutamine-deprived state increases autophagy flux, triggering cancer cell exhaustive death. This effect largely results from the nucleophilic degradation of histone H1.0 and the ensuing unchecked increases in ribosome and protein biosynthesis associated with globally enhanced chromatin accessibility. Intriguingly, IFRD1 depletion in preclinical HCC models synergizes with the treatment of the glutaminase-1 selective inhibitor CB-839 to potentiate the effect of limiting glutamine. Together, our findings reveal how IFRD1 supports the adaptive survival of cancer cells under glutamine starvation, further highlighting the potential of IFRD1 as a therapeutic target in anti-cancer applications.

Caroli disease (CD) is a congenital disease of the intrahepatic biliary system, which manifests as cystic dilatation of the intrahepatic bile ducts. The disease has a low incidence and atypical clinical manifestations; therefore, it can be easily misdiagnosed. Hepatitis B infection is a viral infection that affects liver cells, leading to degeneration, necrosis, and regeneration of the cells and formation of false lobules, and ultimately nodular cirrhosis, which can lead to liver dysfunction and liver failure. Herein, we report a case of decompensated liver cirrhosis because of a diffuse form of CD, which was misdiagnosed because of long-term hepatitis B virus (HBV) infection. Finally, orthotopic liver transplantation (OLT) was performed, and the patient was cured. We believe that this congenital factor combined with HBV infection accelerated cirrhosis progression in this patient. This transplant was carried out in accordance with the Helsinki Congress and the Declaration of Istanbul.

PURPOSE:Pancreatic cancer (PC) is one of the most deadly human malignancies. Curcumin is a natural polyphenolic compound with wide-ranging pharmacological effects. Growing evidence suggests that curcumin has anticancer activity against PC, but the mechanism remains incompletely elucidated. This study aimed to investigate the effects and mechanisms of curcumin on the invasion and migration of PC cells.METHODS:Effect of curcumin on tissue factor pathway inhibitor (TFPI)-2 mRNA expression in PC cells was initially identified using qRT-PCR. Cytotoxicity of curcumin was assessed with MTT assays and IC50 was calculated. Involvement of ERK and JNK pathways, as well as protein expression of TFPI-2 and epithelial-mesenchymal transition (EMT)-related markers, were detected using immunoblotting. Invasion and migration of PC cells were examined using Transwell assays. TFPI-2 expression was manipulated by transfection with siRNA and shRNA. Rescue assays were used to validate the effect of curcumin on cell invasion and migration via TFPI-2.RESULTS:Curcumin increased the expression of TFPI-2 mRNA and protein in PC cells and attenuated cell invasion and migration. Curcumin also inhibited ERK and JNK pathways and EMT in PC cells. Knockdown of TFPI-2 partially reversed the inhibition of ERK and JNK pathways and EMT by curcumin. Mechanistically, curcumin upregulated TFPI-2, thereby inhibiting the ERK and JNK pathways, leading to the inhibition of EMT in PC cells.CONCLUSION:Collectively, curcumin inhibits ERK- and JNK-mediated EMT through upregulating TFPI-2, which in turn suppresses the migration and invasion of PC cells. These findings provide new insights into the antitumor mechanism of curcumin.