Untypical bilateral breast cancer with peritoneal fibrosis on 18F-FDG PET/CT: case report and literature review.

Background: Retroperitoneal fibrosis, a condition of uncertain origin, is rarely linked to 8% of malignant cases, including breast, lung, gastrointestinal, genitourinary, thyroid, and carcinoid. The mechanism leading to peritoneal fibrosis induced by tumors is not well understood, possibly encompassing direct infiltration of neoplastic cells or the initiation of inflammatory responses prompted by cytokines released by tumor cells. We report a case of breast cancer with renal metastasis and retroperitoneal fibrosis detected using 18F-FDG PET/CT, providing help for clinical diagnosis and treatment. Case report: A 49-year-old woman was referred to the hospital with elevated creatinine and oliguria for over a month. Abdominal computer tomography (CT) and magnetic resonance imaging (MRI) showed a retroperitoneal fibrosis-induced acute kidney injury (AKI) was suspected. However, a percutaneous biopsy of the kidney lesion confirmed metastasis from breast cancer. The physical examination revealed inverted nipples and an orange peel appearance on the skin of both breasts. Ultrasonography revealed bilateral hyperplasia (BIRADS 4a) of the mammary glands and bilateral neck and axillary lymphadenopathy. Subsequently, 18F-deoxyglucose positron emission tomography/computer tomography (18F-FDG PET/CT) detected abnormally high uptake (SUVmax) in the bilateral mammary glands and axillary lymph nodes, suggesting bilateral breast cancer. Furthermore, abnormal 18F-FDG uptake was detected in the kidney, suggesting renal metastasis. In addition, abnormal 18F-FDG uptake was observed in the vertebrae, accompanied by an elevation in inhomogeneous bone mineral density, raising suspicion of bone metastases. However, the possibility of myelodysplasia cannot be dismissed, and further investigations will be conducted during close follow-ups. There was significant 18F-FDG uptake in the retroperitoneal position indicating a potential association between retroperitoneal fibrosis and breast cancer. The final pathological diagnosis of the breast tissue confirmed bilateral invasive ductal carcinoma. The patient had been treated with 11 cycles of albumin-bound (nab)-paclitaxel (0.3 mg) and had no significant adverse reaction. Conclusion: In this case, neither the bilateral breast cancer nor the kidney metastatic lesion showed typical nodules or masses, so breast ultrasound, abdominal CT, and MRI did not suggest malignant lesions. PET/CT played an important role in detecting occult metastases and primary lesions, thereby contributing to more accurate staging, monitoring treatment responses, and prediction of prognosis in breast cancer.

Single-Cell multiomics reveals ENL mutation perturbs kidney developmental trajectory by rewiring gene regulatory landscape.

Cell differentiation during organogenesis relies on precise epigenetic and transcriptional control. Disruptions to this regulation can result in developmental abnormalities and malignancies, yet the underlying mechanisms are not well understood. Wilms tumors, a type of embryonal tumor closely linked to disrupted organogenesis, harbor mutations in epigenetic regulators in 30-50% of cases. However, the role of these regulators in kidney development and pathogenesis remains unexplored. By integrating mouse modeling, histological characterizations, and single-cell transcriptomics and chromatin accessibility profiling, we show that a Wilms tumor-associated mutation in the chromatin reader protein ENL disrupts kidney development trajectory by rewiring the gene regulatory landscape. Specifically, the mutant ENL promotes the commitment of nephron progenitors while simultaneously restricting their differentiation by dysregulating key transcription factor regulons, particularly the HOX clusters. It also induces the emergence of abnormal progenitor cells that lose their chromatin identity associated with kidney specification. Furthermore, the mutant ENL might modulate stroma-nephron interactions via paracrine Wnt signaling. These multifaceted effects caused by the mutation result in severe developmental defects in the kidney and early postnatal mortality in mice. Notably, transient inhibition of the histone acetylation binding activity of mutant ENL with a small molecule displaces transcriptional condensates formed by mutant ENL from target genes, abolishes its gene activation function, and restores developmental defects in mice. This work provides new insights into how mutations in epigenetic regulators can alter the gene regulatory landscape to disrupt kidney developmental programs at single-cell resolution in vivo . It also offers a proof-of-concept for the use of epigenetics-targeted agents to rectify developmental defects.

Unraveling the tumor immune microenvironment of lung adenocarcinoma using single-cell RNA sequencing.

Tumor immune microenvironment (TIME) and its indications for lung cancer patient prognosis and therapeutic response have become new hotspots in cancer research in recent years. Tumor cells, immune cells, various regulatory factors, and their interactions in the TIME have been suggested to commonly influence lung cancer development and therapeutic outcome. The heterogeneity of TIME is composed of dynamic immune-related components, including various cancer cells, immune cells, cytokine/chemokine environments, cytotoxic activity, or immunosuppressive factors. The specific composition of cell subtypes may facilitate or hamper the response to immunotherapy and influence patient prognosis. Various markers have been found to stratify the patient prognosis or predict the therapeutic outcome. In this article, we systematically reviewed the recent advancement of TIME studies in lung adenocarcinoma (LUAD) using single-cell RNA sequencing (scRNA-seq) techniques, with specific focuses on the roles of TIME in LUAD development, TIME heterogeneity, indications of TIME in patient prognosis and therapeutic response during immunotherapy and drug resistance. The main findings in TIME heterogeneity and relevant markers or models for prognosis stratification and response prediction have been summarized. We hope that this review provides an overview of TIME status in LUAD and an inspiration for future development of strategies and biomarkers in LUAD treatment.

Enhanced Theranostic Efficacy of 89Zr and 177Lu-Labeled Aflibercept in Renal Cancer: A Viable Option for Clinical Practice.

Vascular endothelial growth factor (VEGF) targeted therapy serves as an important therapeutic approach for renal cancer, but its clinical effectiveness is unsatisfactory. Moreover, there is a lack of reliable biomarkers for preoperative assessment of tumor VEGF expression. This study aimed to explore the potential for further applications of 177Lu/89Zr-labeled aflibercept (Abe), a VEGF-binding agent, in imaging visualization of VEGF expression and therapy for renal cancer. To determine specificity uptake in renal cancer, BALB/c mice with VEGF-expressing Renca tumor were intravenously injected with [89Zr]Zr-Abe, [177Lu]Lu-Abe, or Cy5.5-Abe and the blocking group was designed as a control group. PET, SPECT, and fluorescence images were acquired, and the biodistribution of [89Zr]Zr-Abe and [177Lu]Lu-Abe was performed. Additionally, the [177Lu]Lu-Abe, [177Lu]Lu-Abe-block, 177Lu only, Abe only, and PBS groups were compared for evaluation of the therapeutic effect. To assess the safety, we monitored and evaluated the body weight, blood biochemistry analysis, and whole blood analysis and major organs were stained with hematoxylin and eosin after [177Lu]Lu-Abe treatment. DOTA-Abe was successfully labeled with 177Lu and Df-Abe with 89Zr in our study. The uptake in tumor of [89Zr]Zr-Abe was significantly higher than that of [89Zr]Zr-Abe-block (P < 0.05) and provided excellent tumor contrast in PET images. [177Lu]Lu-Abe demonstrated promising tumor-specific targeting capability with a high and persistent tumor uptake. The standardized tumor volume of [177Lu]Lu-Abe was significantly smaller than those of other treatment groups (P < 0.05). [177Lu]Lu-Abe also had smaller tumor volumes and reduced expression of VEGF and CD31 compared to those of the control groups. Fluorescence images demonstrate higher tumor uptake in the Cy5.5-Abe group compared to the Cy5.5-Abe-block group (P < 0.05). In conclusion, [89Zr]Zr-Abe enables noninvasive analysis of VEGF expression, serving as a valuable tool for assessing the VEGF-targeted therapy effect. Additionally, all of the findings support the enhanced therapeutic efficacy and safety of [177Lu]Lu-Abe, making it a viable option for clinical practice in renal cancer.

Condensate-promoting ENL mutation drives tumorigenesis in vivo through dynamic regulation of histone modifications and gene expression.

Gain-of-function mutations in the histone acetylation 'reader' ENL, found in AML and Wilms tumor, are known to drive condensate formation and gene activation in cellular systems. However, their role in tumorigenesis remains unclear. Using a conditional knock-in mouse model, we show that mutant ENL perturbs normal hematopoiesis, induces aberrant expansion of myeloid progenitors, and triggers rapid onset of aggressive AML. Mutant ENL alters developmental and inflammatory gene programs in part by remodeling histone modifications. Mutant ENL forms condensates in hematopoietic stem/progenitor cells at key leukemogenic genes, and disrupting condensate formation via mutagenesis impairs its chromatin and oncogenic function. Moreover, treatment with an acetyl-binding inhibitor of mutant ENL displaces these condensates from target loci, inhibits mutant ENL-induced chromatin changes, and delays AML initiation and progression in vivo. Our study elucidates the function of ENL mutations in chromatin regulation and tumorigenesis, and demonstrates the potential of targeting pathogenic condensates in cancer treatment.

Molecular Imaging of Fibrosis in Benign Diseases: An Overview of the State of the Art.

Fibrosis is a progressive pathological process participating in the progression of many diseases and can ultimately result in organ malfunction and failure. Around 45% of deaths in the United States are believed to be attributable to fibrotic disorders, and there are no favorable treatment regiments available to meet the need of blocking fibrogenesis, reversing established fibrosis, and curing diseases, especially in the terminal stage. Therefore, early detection and continuous monitoring provide valuable benefits for patients. Among all the advanced techniques developed in recent years for fibrosis evaluation, molecular imaging stands out with its distinct advantage of visualizing biochemical processes and patterns of target localization at the molecular and cellular level. In this review, we summarize the current state of the art in molecular imaging of benign fibrosis diseases. We will first introduce molecular pathways underlying fibrosis processes and potential targets. We will then elaborate on molecular probes that have been developed thus far, expounding on their mechanisms and current states of translational advancement. Finally, we will delineate the extant challenges impeding further progress in this area and the prospective benefits after overcoming these problems.

Minocycline-loaded nHAP/PLGA microspheres for prevention of injury-related corneal angiogenesis.

BACKGROUND: Corneal neovascularization (CoNV) threatens vision by disrupting corneal avascularity, however, current treatments, including pharmacotherapy and surgery, are hindered by limitations in efficacy and adverse effects. Minocycline, known for its anti-inflammatory properties, could suppress CoNV but faces challenges in effective delivery due to the cornea's unique structure. Therefore, in this study a novel drug delivery system using minocycline-loaded nano-hydroxyapatite/poly (lactic-co-glycolic acid) (nHAP/PLGA) nanoparticles was developed to improve treatment outcomes for CoNV. RESULTS: Ultra-small nHAP was synthesized using high gravity technology, then encapsulated in PLGA by a double emulsion method to form nHAP/PLGA microspheres, attenuating the acidic by-products of PLGA degradation. The MINO@PLGA nanocomplex, featuring sustained release and permeation properties, demonstrated an efficient delivery system for minocycline that significantly inhibited the CoNV area in an alkali-burn model without exhibiting apparent cytotoxicity. On day 14, the in vivo microscope examination and ex vivo CD31 staining corroborated the inhibition of neovascularization, with the significantly smaller CoNV area (29.40% ± 6.55%) in the MINO@PLGA Tid group (three times daily) than that of the control group (86.81% ± 15.71%), the MINO group (72.42% ± 30.15%), and the PLGA group (86.87% ± 14.94%) (p < 0.05). Fluorescein sodium staining show MINO@PLGA treatments, administered once daily (Qd) and three times daily (Tid) demonstrated rapid corneal epithelial healing while the Alkali injury group and the DEX group showed longer healing times (p < 0.05). Additionally, compared to the control group, treatments with dexamethasone, MINO, and MINO@PLGA were associated with an increased expression of TGF-ß as evidenced by immunofluorescence, while the levels of pro-inflammatory cytokines IL-1ß and TNF-α demonstrated a significant decrease following alkali burn. Safety evaluations, including assessments of renal and hepatic biomarkers, along with H&E staining of major organs, revealed no significant cytotoxicity of the MINO@PLGA nanocomplex in vivo. CONCLUSIONS: The novel MINO@PLGA nanocomplex, comprising minocycline-loaded nHAP/PLGA microspheres, has shown a substantial capacity for preventing CoNV. This study confirms the complex's ability to downregulate inflammatory pathways, significantly reducing CoNV with minimal cytotoxicity and high biosafety in vivo. Given these findings, MINO@PLGA stands as a highly promising candidate for ocular conditions characterized by CoNV.

An elderly low-grade fibromyxoid sarcoma patient with early postoperative recurrences and metastases: a case report and literature review.

Background: Low-grade fibromyxoid sarcoma (LGFMS) is a rare type of soft tissue sarcoma that often involves the deep soft tissue of the extremities and trunk in young and middle-aged adults. It is uncommon in the elderly. Here we discuss a case of LGFMS in an elderly patient who had recurrence and metastasis within 2 years of resection of the primary tumor. Case report: A 71-year-old LGFMS patient was presented with a mass in the left forearm accompanied by pain and numbness from the left upper arm to fingers. The patient subsequently underwent 3 surgical resections, although she had 3 recurrences within 6 months after the initial diagnosis. Considering the malignant biological behavior of the tumor, an amputation at 5 cm above the elbow was eventually performed. However, recurrence in the extremity of the stump and chest wall metastasis were observed 2 years after amputation. Then resection of the metastases, radiotherapy and particle implantation therapy were performed. The patient is currently undergoing follow-up and has no evidence of recurrence. Conclusion: In our case, multiple early postoperative recurrences may be associated with a positive margin at initial operation. The patient underwent a total of 5 operations including local resection of the primary tumor, twice wide resections, amputation and metastatic surgery with 4 early postoperative recurrences and metastases within 4 years, suggesting that LGFMS may have highly invasive biological behavior. Our case demonstrated that early aggressive surgical treatment is recommended for LGFMS patients with a positive margin at initial operation and patients who had recurrence even after wide resection rather than local resection. Further research is needed to develop more effective treatment options for rapidly progress and highly aggressive LGFMS.

Rapid Fabrication of High-Resolution Flexible Electronics via Nanoparticle Self-Assembly and Transfer Printing.

Printed electronic technology serves as a key component in flexible electronics and wearable devices, yet achieving compatibility with both high resolution and high efficiency remains a significant challenge. Here, we propose a rapid fabrication method of high-resolution nanoparticle microelectronics via self-assembly and transfer printing. The tension gradient-electrostatic attraction composite-induced nanoparticle self-assembly strategy is constructed, which can significantly enhance the self-assembly efficiency, stability, and coverage by leveraging the meniscus Marangoni effect and the electric double-layer effect. The close-packed nanoparticle self-assembly layer can be rapidly formed on microstructure surfaces over a large area. Inspired by ink printing, a transfer printing strategy is further proposed to transform the self-assembly layer into conformal micropatterns. Large-area, high-resolution (2 µm), and ultrathin (1 µm) nanoparticle microelectronics can be stably fabricated, yielding a significant improvement over fluid printing methods. The unique deformability, recoverability, and scalability of nanoparticle microelectronics are revealed, providing promising opportunities for various academic and real applications.

Microarray-Based CD38 Peptide Probe Screening for Multiple Myeloma Imaging.

Assessing CD38 expression in vivo has become a significant element in multiple myeloma (MM) therapy, as it can be used to detect lesions and forecast the effectiveness of treatment. Accurate diagnosis requires a multifunctional, high-throughput probe screening platform to develop molecular probes for tumor-targeted multimodal imaging and treatment. Here, we investigated a microarray chip-based strategy for high-throughput screening of peptide probes for CD38. We obtained two new target peptides, CA-1 and CA-2, from a 105 peptide library with a dissociation constant (KD) of 10-7 M. The specificity and affinity of the target peptides were confirmed at the molecular and cellular levels. Peptide probes were labeled with indocyanine green (ICG) dye and 68Ga-DOTA, which were injected into a CD38-positive Ramos tumor-bearing mouse via its tail vein, and small animal fluorescence and positron emission tomography (PET) imaging showed that the peptide probes could show specific enrichment in the tumor tissue. Our study shows that a microchip-based screening of peptide probes can be used as a promising imaging tool for MM diagnosis.

Theranostic role of 89Zr- and 177Lu-labeled aflibercept in breast cancer.

PURPOSE: Triple-negative breast cancer (TNBC) has a poor prognosis due to the absence of effective therapeutic targets. Vascular endothelial growth factor (VEGF) family are expressed in 30-60% of TNBC, therefore providing potential therapeutic targets for TNBC. Aflibercept (Abe), a humanized recombinant fusion protein specifically bound to VEGF-A, B and placental growth factor (PIGF), has proven to be effective in the treatment in some cancers. Therefore, 89Zr/177Lu-labeled Abe was investigated for its theranostic role in TNBC. METHODS: Abe was radiolabeled with 89Zr and 177Lu via the conjugation of chelators. Flow cytometry and cell immunofluorescent staining were performed to evaluate the binding affinity of Abe. Sequential PET imaging and fluorescent imaging were conducted in TNBC tumor bearing mice following the injection of 89Zr-labeled Abe and Cy5.5-labeled Abe. Treatment study was performed after the administration of 177Lu-labeled Abe. Tumor volume and survival were monitored and SPECT imaging and biodistribution studies were conducted. Safety evaluation was performed including body weight, blood cell measurement, and hematoxylin-eosin (H&E) staining of major organs. Expression of VEGF and CD31 was tested by immunohistochemical staining. Dosimetry was estimated using the OLINDA software. RESULTS: FITC-labeled Abe showed a strong binding affinity to VEGF in TNBC 4T1 cells and HUVECs by flow cytometry and cell immunofluorescence. Tumor uptake of 89Zr-labeled Abe peaked at 120 h (SUVmax = 3.2 ± 0.64) and persisted before 168 h (SUVmax = 2.54 ± 0.42). The fluorescence intensity of the Cy5.5-labeled Abe group surpassed that of the Cy5.5-labeled IgG group, implying that Cy5.5-labeled Abe is a viable candidate monitoring in vivo tumor targeting and localization. 177Lu-labeled Abe (11.1 MBq) served well as the therapeutic component to suppress tumor growth with standardized tumor volume at 16 days, significantly smaller than PBS group (about 815.66 ± 3.58% vs 3646.52 ± 11.10%, n = 5, P < 0.01). Moreover, SPECT images confirmed high contrast between tumors and normal organs, indicating selective tumor uptake of 177Lu-labeled Abe. No discernible abnormalities in blood cells, and no evident histopathological abnormality observed in liver, spleen, and kidney. Immunohistochemical staining showed that 177Lu-labeled Abe effectively inhibited the expression of VEGF and CD31 of tumor, suggesting that angiogenesis may be suppressed by 177Lu-labeled Abe. The whole-body effective dose for an adult human was estimated to be 0.16 mSv/MBq. CONCLUSION: 89Zr/177Lu-labeled Abe could be a TNBC-specific marker with diagnostic value and provide insights into targeted therapy in the treatment of TNBC. Further clinical evaluation and translation may be of high significance for TNBC.

CD146-targeted nuclear medicine imaging in cancer: state of the art.

The transmembrane glycoprotein adhesion molecule CD146 is overexpressed in a wide variety of cancers. Through molecular imaging, a specific biomarker's expression and distribution can be viewed in vivo non-invasively. Radionuclide-labeled monoclonal antibodies or relevant fragments that target CD146 may find potential applications in cancer imaging, thereby offering tremendous value in cancer diagnosis, staging, prognosis evaluation, and prediction of drug resistance. This review discusses the recent developments of CD146-targeted molecular imaging via nuclear medicine, especially in malignant melanoma, brain tumor, lung cancer, liver cancer, breast cancer, and pancreatic cancer. Many studies have proved that CD146 targeting may present a promising strategy for cancer theranostics.

Case Report: A rare case of multicentric angiosarcomas of bone mimicking multiple myeloma on 18F-FDG PET/CT.

Background: Angiosarcoma, a rare endothelial-origin tumor, can develop throughout the body, with the head and neck skin being the most commonly affected areas. It can also originate in other sites such as the breast, iliac artery, and visceral organs including the liver, spleen, and kidneys. Angiosarcoma of the bone is remarkably rare, presenting as either unifocal or multifocal bone lesions and often leading to a grim prognosis. Diagnosing bone angiosarcoma poses a significant challenge. 18F-FDG PET/CT serves as a reliable and indispensable imaging modality for evaluating distant metastases and clinically staging angiosarcomas. Case report: A 57-year-old woman presented with a 10-day history of dizziness and headaches. Cranial CT scan revealed bone destruction of the parietal bone, accompanied by soft tissue lesions, protruding into the epidural space. MRI examination demonstrated lesions with slightly elevated signal intensity on T2FLAIR, showing moderate enhancement. Furthermore, multiple foci were observed within the T12, L1-5, and S1-2 vertebrae, as well as in the bilateral iliac bones. For staging, 18F-FDG PET/CT was performed. The MIP PET showed multifocal FDG-avid lesions in the sternum, bilateral clavicles, bilateral scapulae, multiple ribs, and pelvic bones. Heterogeneous FDG uptake was observed in multiple bone lesions, including intracranial (SUVmax = 11.3), right transverse process of the T10 vertebra (SUVmax = 5.8), ilium (SUVmax = 3.3), and pubis (SUVmax = 4.7). The patient underwent surgical resection of the cranial lesion. The pathological diagnosis was made with a highly differentiated angiosarcoma. Conclusion: Angiosarcoma of bone on FDG PET/CT scans is characterized by abnormal FDG uptake along with osteolytic destruction. This case highlights that angiosarcoma of bone can manifest as multicentric FDG uptake, resembling the pattern seen in multiple myeloma. FDG PET/CT can be a useful tool for staging this rare malignant tumor, offering the potential to guide biopsy procedures toward the most metabolically active site. And it should be considered in the differential diagnosis of multiple osteolytic lesions, including metastatic carcinoma, multiple myeloma, and lymphoma of bone.

Scribble deficiency mediates colon inflammation by inhibiting autophagy-dependent oxidative stress elimination.

Scribble is a master scaffold protein in apical-basal polarity. Current knowledge about the biological function of Scribble in colonic epithelial plasticity/regeneration during intestinal inflammation is limited. Here, we showed that the level of Scribble is decreased in inflammatory bowel disease (IBD) patients and mice with DSS-induced colitis. ScribΔIEC mice develops severe acute colitis with disrupted epithelial barrier integrity and impaired crypt stem cell's function. Mechanistically, Scribble suppressed the process of autophagy by modulating the stability of caspase-dependent degradation of Atg16L1 by directly interacting with Atg16L1 in a LRR domain-dependent manner in IECs and led to an accumulation of ROS both in intestinal stem cells and epithelial cells. In addition, further study indicates that dietary sphingomyelin alleviates DSS-induced colitis by increase the expression of Scribble, which suggests that Scribble may be the critical marker of IBD. Our study shows that Scribble deficiency is associated with the dysregulated autophagy and impaired maintenance of colonic stemness, and it may be a target for diagnosis and treatment of IBD.

Duodenal-type follicular lymphoma in 18F-FDG PET/CT imaging: a case report.

Follicular lymphoma (FL) is a subtype of non-Hodgkin lymphoma (NHL) that is typically characterized by a slow-growing course. Duodenal-type follicular lymphoma (D-FL) was recently reclassified as a distinct variant. This subtype exhibits unique clinical and biological characteristics, which set it apart from other forms of FL. We report a case of a 36-year-old male patient with multiple, small, gray polypoid lesions in the descending duodenum which were detected by esophagogastroduodenoscopy. The pathological diagnosis was low-grade D-FL. 18F-FDG PET/CT was performed for staging and revealed the pancreas and peripheral lymph nodes were involved by FL, with a clinical IV stage. The patient underwent a bone marrow smear cytology, which revealed no bone marrow abnormalities, and excluded bone marrow involvement. He was treated with six cycles of chemotherapy using the R-CHOP regimen and reached complete remission.

Scribble promotes fibrosis-dependent mechanisms of hepatocarcinogenesis by p53/PUMA-mediated glycolysis.

BACKGROUNDS AND AIMS: Liver cancer is the sixth most common type of cancer and the fifth leading cause of cancer mortality worldwide. Scribble has been shown to function as a neoplastic tumor suppressor gene in most tumors. Our previous studies reported that down-regulation or mislocalization of Scribble was sufficient to initiate mammary tumorigenesis and NSCLC. Recently, it was reported that Scribble was highly expressed in hepatocellular carcinoma (HCC). We aim to study how it was up-regulated and the contradictory role of Scribble in HCC. METHODS AND RESULTS: Using a mouse model of carbon tetrachloride (CCl4)-induced liver fibrosis system, we showed that Scribble was over-expressed and which may protect the mice against hepatic fibrosis. Unexpectedly, we found out the potential for Scribble to act as a tumor driver at the advanced stage of N-nitrosodiethylamine (DEN) plus CCl4 induced HCC mice model in vivo. In addition, we observed even higher expression of Scribble in HCC tumors harboring elevated levels of wild-type p53. Most importantly, nuclear translocated Scribble could interact with p53, which lead to enhanced stability and transcriptional activity of p53. Mechanistically, our data suggested that Scribble might drive HCC progression by promoting metabolic regulation of p53 through p53-upregulated modulator of apoptosis (PUMA)-mediated Warburg effect. CONCLUSIONS: Our data identified the molecular basis of hepatic fibrosis-specific gene expression of polarity gene, such as Scribble. Interestingly, with the progression from fibrosis to cirrhosis to HCC, its nuclear translocation promoted a wild-type p53-mediated cancer metabolic switch and tumor progression in HCC. Taken together, we demonstrated that Scribble was up-regulated and served a protective role in liver fibrosis, while also apparently acting as a tumor driver in fibrosis-dependent hepatocarcinogenesis.

Diagnostic and Prognostic Performance of MicroRNA-25, Carbohydrate Antigen 19-9, Carcinoembryonic Antigen, and Carbohydrate Antigen 125 in Pancreatic Ductal Adenocarcinoma.

Background: Pancreatic cancer is a malignancy with high mortality due to the difficulties in early detection. We investigated and compared the diagnostic and prognostic performance of several blood biomarkers, including microRNA-25 (miR-25), carbohydrate antigen 19-9 (CA19-9), carcinoembryonic antigen (CEA), and carbohydrate antigen 125 (CA125). Methods: A retrospective study was conducted at the Chinese People's Liberation Army General Hospital from May 2014 to September 2018. Serum specimens were collected, and miR-25 expression levels were measured using real-time quantitative polymerase chain reaction. Serum CA19-9, CEA, and CA125 levels were measured using enzyme-linked immunosorbent assay (ELISA). Statistical analyses including nonparametric test, receiver operator characteristic (ROC) curves, Kaplan-Meier analysis, and subsequent log-rank test were performed with PRISM 5.0 software. Univariate and multivariate analyses were performed with the R software. P<0.05 was considered statistically significant. Results: A total of 250 individuals were recruited, including 75 with pancreatic ductal adenocarcinoma (PDAC), 75 with benign lesions, and 100 healthy controls. miR-25, CA19-9, CEA, and CA125 exhibited an area under the curve (AUC) of 0.88, 0.91, 0.81, and 0.76 with a sensitivity of 78.7%, 74.7%, 37.3%, and 35.7% and specificity of 91.5%, 97.0%, 98.2%, and 98.3%, respectively. The combination of miR-25 and CA19-9 further increased the sensitivity to 93.3% with a specificity of 88.5%. Stage-dependent sensitivity was observed with CA19-9, CEA, and CA125. miR-25 levels significantly stratified the prognosis by median level (4,989.97 copies/mL). CA19-9, CEA, and CA125 levels significantly stratified the prognosis by median levels. Univariate and subsequent multivariate analyses identified tumor (T) stage, CA19-9, and CA125 as independent risk factors for PDAC prognosis. Conclusion: The combination of miR-25 and CA19-9 significantly enhanced the detection sensitivity of PDAC. T stage, CA19-9, and CA125 levels were independent risk factors for PDAC prognosis.

Establishing Transition Metal Phosphides as Effective Sulfur Hosts in Lithium-Sulfur Batteries through the Triple Effect of "Confinement-Adsorption-Catalysis".

Structurally optimized transition metal phosphides are identified as a promising avenue for the commercialization of lithium-sulfur (Li-S) batteries. In this study, a CoP nanoparticle-doped hollow ordered mesoporous carbon sphere (CoP-OMCS) is developed as a S host with a "Confinement-Adsorption-Catalysis" triple effect for Li-S batteries. The Li-S batteries with CoP-OMCS/S cathode demonstrate excellent performance, delivering a discharge capacity of 1148 mAh g-1 at 0.5 C and good cycling stability with a low long-cycle capacity decay rate of 0.059% per cycle. Even at a high current density of 2 C after 200 cycles, a high specific discharge capacity of 524 mAh g-1 is maintained. Moreover, a reversible areal capacity of 6.56 mAh cm-2 is achieved after 100 cycles at 0.2 C, despite a high S loading of 6.8 mg cm-2 . Density functional theory (DFT) calculations show that CoP exhibits enhanced adsorption capacity for sulfur-containing substances. Additionally, the optimized electronic structure of CoP significantly reduces the energy barrier during the conversion of Li2 S4 (L) to Li2 S2 (S). In summary, this work provides a promising approach to optimize transition metal phosphide materials structurally and design cathodes for Li-S batteries.