High cure rate and satisfaction in patients with periductal mastitis via the latissimus dorsi myocutaneous flap technique: a retrospective study.

Background: Periductal mastitis (PDM) is a complex benign breast disease with a prolonged course and a high probability of recurrence after treatment. There is a variety of available treatments for PDM, but none of these options have been widely accepted. A standard strategy has been especially difficult to establish in patients with PDM accompanied by large tumors or large skin ruptures, as these seriously affect the appearance of the breasts after surgeries, which can lead to feelings of lower self-esteem among patients. Therefore, finding a reliable volume replacement has become a focus of our research efforts. With the widespread use of latissimus dorsi in breast reconstruction, we attempted to use the latissimus muscle (skin) flap for stage I repair in patients with large-defect PDM. Our study is the first of its kind to evaluate the clinical effect and patient satisfaction of the latissimus dorsi myocutaneous flap (LDMF) technique in PDM. Methods: Thirty-two patients with PDM and more than about 20% loss of breast volume admitted to the Department of Breast Surgery of Shanxi Bethune Hospital from March 2017 to July 2021 were enrolled. After lesion removal, the LDMF technique was applied to these patients for immediate completion of breast contour revision. All patients were periodically followed up to assess the efficacy of the procedure and their satisfaction with the breasts' shape. Results: Three patients (9.4%) developed dorsal effusion after removal of the back drain; six patients (18.8%) developed mild limitation of the activity of the affected upper limb; and three patients (9.4%) experienced local recurrence of inflammation after the operation, all of whom underwent a second operation. The cure rate of the patients treated with LDMF was 90.6%, the overall satisfaction rate of the patients was 96.9%, and doctor's evaluation of satisfaction was 90.6%. Conclusions: In patients with poor results after anti-infective and local treatment and those with more than 20% defect volume following lesion removal, the LDMF technique yields a high cure rate and good patient satisfaction.

Comparison of 18F-FDG PET/CT and 18F-DOTATATE PET/CT in the diagnosis of multiple metastases in rectal neuroendocrine neoplasms.

This case report describes a 62-year-old male with a notable medical history, including surgically treated bladder cancer and the suspicion of metastatic disease. He underwent 18F-FDG PET/CT imaging as part of the initial diagnostic workup, which identified several marginally hypodense hepatic lesions. These lesions exhibited metabolic activity that was slightly lower than the surrounding hepatic parenchyma, raising concerns for metastatic involvement. Subsequent 18F-DOTATATE PET/CT imaging significantly expanded the diagnostic perspective by identifying multiple somatostatin receptor (SSTR)-positive lesions, not only in the liver but also in lymph nodes and bones. This marked an important diagnostic advancement over the initial FDG PET/CT findings, showcasing the superior sensitivity of 18F-DOTATATE PET/CT in detecting SSTR-expressing tumors. Pathological evaluation after these imaging studies confirmed the diagnosis of a rectal neuroendocrine tumor (NET) with extensive hepatic metastasis, altering the clinical management and therapeutic approach for the patient. This case underscores the pivotal role of integrating 18F-DOTATATE and FDG PET/CT in the diagnostic and therapeutic management of neuroendocrine tumors, highlighting the complementary nature of these imaging modalities. The findings advocate for the use of 18F-DOTATATE PET/CT in cases where NETs are suspected, particularly for its enhanced sensitivity in detecting SSTR-positive lesions across various sites, thereby facilitating a more comprehensive disease assessment and informed therapeutic planning.

The first-in-human preclinical evaluation of the new probe [123I]I-PSMA-7 for real-time intraoperative targeted biopsy and SPECT/CT imaging in prostate cancer.

PURPOSE: PSMA/PET has been increasingly used to detect PCa, and PSMA/PET-guided biopsy has shown promising results. However, it cannot be confirmed immediately whether the tissues are the targeted area. In this study, we aimed to develop a novel probe, [123I]I-PSMA-7. First, we hope that [123I]I-PSMA-7 can provide instant confirmation for prostate biopsy. Second, we hope it will help detect PCa. METHODS: We synthesized a high-affinity probe, [123I]I-PSMA-7, and evaluated its properties. We included ten patients with suspected PCa and divided them into two groups. The injection and biopsy were approximately 24 h apart. The activity in biopsy lesions was measured as the cpm by a γ-counter. Moreover, we enrolled 3 patients to evaluate the potential of [123I]I-PSMA-7 for detecting PCa. RESULTS: Animal experiments verified the safety, targeting and effectiveness of [123I]I-PSMA-7, and the tumor-to-muscle ratio was greatest at 24 h, which confirmed the results of this study in humans. After injection of 185MBq [123I]I-PSMA-7, 18/55 cores were positive, and the cpm was significantly greater (4345 ± 3547 vs. 714 ± 547, P < 0.001), with an AUC of 0.97 and a cutoff of 1312 (sens/spec of 94.40%/91.90%). At a lower dose, 10/55 biopsy cores were cancerous, and the cpm was 2446 ± 1622 vs. 153 ± 112 (P < 0.001). The AUC was 1, with a cutoff value of 490 (sens/spec of 100%). When the radiopharmaceuticals were added to 370 MBq, we achieved better SPECT/CT imaging. CONCLUSION: With the aid of [123I]I-PSMA-7 and via cpm-based biopsy, we can reduce the number of biopsies to a minimum operation. [123I]I-PSMA-7 PSMA SPECT/CT can also provide good imaging results. TRIAL REGISTRATION: Chinese Clinical trial registry ChiCTR2300069745, Registered 24 March 2023.

Metagenome-assembled bacterial genomes derived from various aging flue-cured tobacco samples.

We recovered 16 bacterial metagenome-assembled genomes from 11 flue-cured tobacco samples with different aging stage and various geographic origins. Their sizes range from 2.3 M to 5.4 M, with GC contents of 43.17%-74.45%, completeness of 78.80%-99.25%, and contamination of 0.47%-8.56%.

A Renal Clearable Nano-Assembly with Förster Resonance Energy Transfer Amplified Superoxide Radical and Heat Generation to Overcome Hypoxia Resistance in Phototherapeutics.

Given that type I photosensitizers (PSs) possess a good hypoxic tolerance, developing an innovative tactic to construct type I PSs is crucially important, but remains a challenge. Herein, we present a smart molecular design strategy based on the Förster resonance energy transfer (FRET) mechanism to develop a type I photodynamic therapy (PDT) agent with an encouraging amplification effect for accurate hypoxic tumor therapy. Of note, benefiting from the FRET effect, the obtained nanostructured type I PDT agent (NanoPcSZ) with boosted light-harvesting ability not only amplifies superoxide radical (O2•-) production but also promotes heat generation upon near-infrared light irradiation. These features facilitate NanoPcSZ to realize excellent phototherapeutic response under both normal and hypoxic environments. As a result, both in vitro and in vivo experiments achieved a remarkable improvement in therapeutic efficacy via the combined effect of photothermal action and type I photoreaction. Notably, NanoPcSZ can be eliminated from organs (including the liver, lung, spleen, and kidney) apart from the tumor site and excreted through urine within 24 h of its systemic administration. In this way, the potential biotoxicity of drug accumulation can be avoided and the biosafety can be further enhanced.

AKT1 Promotes Tumorigenesis and Metastasis by Directly Phosphorylating Hexokinases.

The importance of protein kinase B (AKT) in tumorigenesis and development is well established, but its potential regulation of metabolic reprogramming via phosphorylation of the hexokinase (HK) isozymes remains unclear. There are two HK family members (HK1/2) and three AKT family members (AKT1/2/3), with varied distribution of AKTs exhibiting distinct functions in different tissues and cell types. Although AKT is known to phosphorylate HK2 at threonine 473, AKT-mediated phosphorylation of HK1 has not been reported. We examined direct binding and phosphorylation of HK1/2 by AKT1 and identified the phosphorylation modification sites using coimmunoprecipitation, glutathione pull-down, western blotting, and in vitro kinase assays. Regulation of HK activity through phosphorylation by AKT1 was also examined. Uptake of 2-[1,2-3H]-deoxyglucose and production of lactate were investigated to determine whether AKT1 regulates glucose metabolism by phosphorylating HK1/2. Functional assays, immunohistochemistry, and tumor experiments in mice were performed to investigate whether AKT1-mediated regulation of tumor development is dependent on its kinase activity and/or the involvement of HK1/2. AKT interacted with and phosphorylated HK1 and HK2. Serine phosphorylation significantly increased AKT kinase activity, thereby enhancing glycolysis. Mechanistically, the phosphorylation of HK1 at serine 178 (S178) by AKT significantly decreased the Km and enhanced the Vmax by interfering with the formation of HK1 dimers. Mutations in the AKT phosphorylation sites of HK1 or HK2 significantly abrogated the stimulatory characteristics of AKT on glycolysis, tumorigenesis, and cell migration, invasion, proliferation, and metastasis. HK1-S178 phosphorylation levels were significantly correlated with the occurrence and metastasis of different types of clinical tumors. We conclude that AKT not only regulates tumor glucose metabolism by directly phosphorylating HK1 and HK2, but also plays important roles in tumor progression, proliferation, and migration.

Mn-based Prussian blue analogues: Multifunctional nanozymes for hydrogen peroxide detection and photothermal therapy of tumors.

Nanozymes have the advantages of simple synthesis, high stability, low cost and easy recycling, and can be applied in many fields including molecular detection, disease diagnosis and cancer therapy. However, most of the current nanozymes suffer from the defects of low catalytic activity and single function, which limits their sensing sensitivity and multifunctional applications. The development of highly active and multifunctional nanozymes is an important way to realize multidisciplinary applications. In this work, Mn-based Prussian blue analogues (Mn-PBA) and their derived double-shelled nanoboxes (DSNBs) are synthesized by co-precipitation method. The nanobox structure of DSNBs formed by etching Mn-PBA with tannic acid endows Mn-PBA DSNBs with better peroxidase-like activity than Mn-PBA. A colorimetric method for the rapid and sensitive determination of H2O2 is developed using Mn-PBA DSNBs-1.5 as a sensor with a detection limit as low as 0.62 µM. Moreover, Mn-PBA DSNBs-2 has excellent photothermal conversion ability, which can be applied to the photothermal therapy of tumors to inhibit the proliferation of tumor cells without damaging other tissues and organs. This study provides a new idea for the rational design of nanozymes and the expansion of their multi-functional applications in various fields.

Mechanisms of tumor immunosuppressive microenvironment formation in esophageal cancer.

As a highly invasive malignancy, esophageal cancer (EC) is a global health issue, and was the eighth most prevalent cancer and the sixth leading cause of cancer-related death worldwide in 2020. Due to its highly immunogenic nature, emer-ging immunotherapy approaches, such as immune checkpoint blockade, have demonstrated promising efficacy in treating EC; however, certain limitations and challenges still exist. In addition, tumors may exhibit primary or acquired resistance to immunotherapy in the tumor immune microenvironment (TIME); thus, understanding the TIME is urgent and crucial, especially given the im-portance of an immunosuppressive microenvironment in tumor progression. The aim of this review was to better elucidate the mechanisms of the suppressive TIME, including cell infiltration, immune cell subsets, cytokines and signaling pathways in the tumor microenvironment of EC patients, as well as the downregulated expression of major histocompatibility complex molecules in tumor cells, to obtain a better understanding of the differences in EC patient responses to immunotherapeutic strategies and accurately predict the efficacy of immunotherapies. Therefore, personalized treatments could be developed to maximize the advantages of immunotherapy.

Nanoparticles for inducing Gaucher disease-like damage in cancer cells.

Nutrient avidity is one of the most distinctive features of tumours. However, nutrient deprivation has yielded limited clinical benefits. In Gaucher disease, an inherited metabolic disorder, cells produce cholesteryl-glucoside which accumulates in lysosomes and causes cell damage. Here we develop a nanoparticle (AbCholB) to emulate natural-lipoprotein-carried cholesterol and initiate Gaucher disease-like damage in cancer cells. AbCholB is composed of a phenylboronic-acid-modified cholesterol (CholB) and albumin. Cancer cells uptake the nanoparticles into lysosomes, where CholB reacts with glucose and generates a cholesteryl-glucoside-like structure that resists degradation and aggregates into microscale crystals, causing Gaucher disease-like damage in a glucose-dependent manner. In addition, the nutrient-sensing function of mTOR is suppressed. It is observed that normal cells escape severe damage due to their inferior ability to compete for nutrients compared with cancer cells. This work provides a bioinspired strategy to selectively impede the metabolic action of cancer cells by taking advantage of their nutrient avidity.

Gold Nanoparticle Delivery of Glut1 SiRNA Facilitates Glucose Starvation Therapy in Lung Cancer.

Glucose transporter protein-1 (Glut1), is highly expressed in many cancer types and plays a crucial role in cancer progression through enhanced glucose transport. Its overexpression is associated with aggressive tumor behavior and poor prognosis. Herein, the nucleic acids modified gold nanoparticles (AuNPs) was synthesized to deliver small interfering RNA (siRNA) against Glut1 by microRNA 21 (miR-21) triggers toehold-mediated strand displacement reaction for lung cancer starvation therapy. Overexpression of miR-21 triggers toehold-mediated strand displacement, releasing the siRNA to knockdown of Glut1 in cancer cell instead of normal cell. Furthermore, the glucose oxidase-like activity of the AuNPs accelerates intracellular glucose consumption, promoting cancer cell starvation. The engineered AuNPs@anti-miR-21/siGlut1 complex inhibits cancer cell proliferation, xenograft tumor growth and promotes apoptosis through glucose starvation and ROS cascade signaling, underscoring its potential as an effective therapeutic strategy for lung cancer.

Synthesis and Evaluation of [18F]AlF-NOTA-c-DVAP: A Novel PET Probe for Imaging GRP78 in Cancer.

GRP78, a member of the HSP70 superfamily, is an endoplasmic reticulum chaperone protein overexpressed in various cancers, making it a promising target for cancer imaging and therapy. Positron emission tomography (PET) imaging offers unique advantages in real time, noninvasive tumor imaging, rendering it a suitable tool for targeting GRP78 in tumor imaging to guide targeted therapy. Several studies have reported successful tumor imaging using PET probes targeting GRP78. However, existing PET probes face challenges such as low tumor uptake, inadequate in vivo distribution, and high abdominal background signal. Therefore, this study introduces a novel peptide PET probe, [18F]AlF-NOTA-c-DVAP, for targeted tumor imaging of GRP78. [18F]AlF-NOTA-c-DVAP was radiolabeled with fluoride-18 using the aluminum-[18F]fluoride ([18F]AlF) method. The study assessed the partition coefficients, stability in vitro, and metabolic stability of [18F]AlF-NOTA-c-DVAP. Micro-PET imaging, pharmacokinetic analysis, and biodistribution studies were carried out in tumor-bearing mice to evaluate the probe's performance. Docking studies and pharmacokinetic analyses of [18F]AlF-NOTA-c-DVAP were also performed. Immunohistochemical and immunofluorescence analyses were conducted to confirm GRP78 expression in tumor tissues. The probe's binding affinity to GRP78 was analyzed by molecular docking simulation. [18F]AlF-NOTA-c-DVAP was radiolabeled in just 25 min with a high yield of 51 ± 16%, a radiochemical purity of 99%, and molar activity within the range of 20-50 GBq/µmol. [18F]AlF-NOTA-c-DVAP demonstrated high stability in vitro and in vivo, with a logD value of -3.41 ± 0.03. Dynamic PET imaging of [18F]AlF-NOTA-c-DVAP in tumors showed rapid uptake and sustained retention, with minimal background uptake. Biodistribution studies revealed rapid blood clearance and excretion through the kidneys following a single-compartment reversible metabolic model. In PET imaging, the T/M ratios for A549 tumors (high GRP78 expression), MDA-MB-231 tumors (medium expression), and HepG2 tumors (low expression) at 60 min postintravenous injection were 10.48 ± 1.39, 6.25 ± 0.47, and 3.15 ± 1.15% ID/g, respectively, indicating a positive correlation with GRP78 expression. This study demonstrates the feasibility of using [18F]AlF-NOTA-c-DVAP as a PET tracer for imaging GRP78 in tumors. The probe shows promising results in terms of stability, specificity, and tumor targeting. Further research may explore the clinical utility and potential therapeutic applications of this PET tracer for cancer diagnosis.

Pan-cancer and multi-omics analyses revealed the diagnostic and prognostic value of BAZ2A in liver cancer.

BAZ2A, an epigenetic regulatory factor that affects ribosomal RNA transcription, has been shown to be highly expressed in several cancers and promotes tumor cell migration. This study explored the expression and mechanism of BAZ2A in tumorigenesis at the pan-cancer level. The Cancer Genome Atlas, Gene Expression Omnibus databases and TIMER2.0, cBioPortal and other tools were used to analyze the level of expression of BAZ2A in various tumor tissues and to examine the relationship between BAZ2A and survival, prognosis, mutation and immune invasion. In vitro experiments were performed to assess the function of BAZ2A in cancer cells. Using combined transcriptome and proteome analysis, we examined the possible mechanism of BAZ2A in tumors. BAZ2A exhibited high expression levels in multiple tumor tissues and displayed a significant association with cancer patient prognosis. The main type of BAZ2A genetic variation in cancer is gene mutation. Downregulation of BAZ2A inhibited proliferation, migration, and invasion and promoted apoptosis in LM6 liver cancer cell. The mechanism of BAZ2A in cancer development may involve lipid metabolism. These results help expand our understanding of BAZ2A in tumorigenesis and development and suggest BAZ2A may serve as a prognostic and diagnostic factor in several cancers.

A NAD(P)H oxidase mimic for catalytic tumor therapy via a deacetylase SIRT7-mediated AKT/GSK3ß pathway.

Nicotinamide adenine dinucleotide (NADH) and its phosphorylated form, NADPH, are essential cofactors that play critical roles in cell functions, influencing antioxidation, reductive biosynthesis, and cellular pathways involved in tumor cell apoptosis and tumorigenesis. However, the use of nanomaterials to consume NAD(P)H and thus bring an impact on signaling pathways in cancer treatment remains understudied. In this study, we employed a salt template method to synthesize a carbon-coated-cobalt composite (C@Co) nanozyme, which exhibited excellent NAD(P)H oxidase (NOX)-like activity and mimicked the reaction mechanism of natural NOX. The C@Co nanozyme efficiently consumed NAD(P)H within cancer cells, leading to increased production of reactive oxygen species (ROS) and a reduction in mitochondrial membrane potential. Meanwhile, the generation of the biologically active cofactor NAD(P)+ promoted the expression of the deacetylase SIRT7, which in turn inhibited the serine/threonine kinase AKT signaling pathway, ultimately promoting apoptosis. This work sheds light on the influence of nanozymes with NOX-like activity on cellular signaling pathways in tumor therapy and demonstrates their promising antitumor effects in a tumor xenograft mouse model. These findings contribute to a better understanding of NAD(P)H manipulation in cancer treatment and suggest the potential of nanozymes as a therapeutic strategy for cancer therapy.

Synthesis and preclinical evaluation of a novel PET/fluorescence dual-modality probe targeting fibroblast activation protein.

Early diagnosis and precise surgical intervention are crucial for cancer patients. We aimed to develop a novel positron emission tomography (PET)/fluorescence dual-modality probe for preoperative diagnosis, intraoperative guidance, and postoperative monitoring of fibroblast activation protein (FAP)-positive tumors. FAPI-FAM was synthesized and labeled with gallium-68. [68Ga]Ga-FAPI-FAM showed favorable in vivo and in vitro characteristics, specific binding affinity, and excellent tumor accumulation in FAP-positive cells and mice xenografts. Excellent tumor-to-background contrast was found owing to high tumor uptake, prolonged retention, and rapid renal clearance of [68Ga]Ga-FAPI-FAM. Moreover, a specific fluorescence signal was detected in FAP-positive tumors during ex vivo fluorescence imaging, demonstrating the feasibility of whole-body tumor detection and intraoperative tumor delineation.

Green Synthesis of Narrow-Size Silver Nanoparticles Using Ginkgo biloba Leaves: Condition Optimization, Characterization, and Antibacterial and Cytotoxic Activities.

Natural products derived from medicinal plants offer convenience and therapeutic potential and have inspired the development of antimicrobial agents. Thus, it is worth exploring the combination of nanotechnology and natural products. In this study, silver nanoparticles (AgNPs) were synthesized from the leaf extract of Ginkgo biloba (Gb), having abundant flavonoid compounds. The reaction conditions and the colloidal stability were assessed using ultraviolet-visible spectroscopy. X-ray diffraction, transmission electron microscopy, and Fourier transform infrared spectroscopy (FTIR) were used to characterize the AgNPs. AgNPs exhibited a spherical morphology, uniform dispersion, and diameter ranging from ~8 to 9 nm. The FTIR data indicated that phytoconstituents, such as polyphenols, flavonoids, and terpenoids, could potentially serve as reducing and capping agents. The antibacterial activity of the synthesized AgNPs was assessed using broth dilution and agar well diffusion assays. The results demonstrate antibacterial effects against both Gram-positive and Gram-negative strains at low AgNP concentrations. The cytotoxicity of AgNPs was examined in vitro using the CCK-8 method, which showed that low concentrations of AgNPs are noncytotoxic to normal cells and promote cell growth. In conclusion, an environmentally friendly approach for synthesizing AgNPs from Gb leaves yielded antibacterial AgNPs with minimal toxicity, holding promise for future applications in the field of biomedicine.

Structure and function analyses of the SRC gene in Pacific white shrimp Litopenaeus vannamei.

SRC gene encodes scavenger receptor class C, a member of the scavenger receptor family, and has only been identified and investigated in invertebrates. Our previous studies have revealed that SRC is a novel candidate gene associated with body weight in Pacific white shrimp (Litopenaeus vannamei). In order to comprehend the underlying mechanism by which LvSRC affects shrimp growth, we analyzed the structure, phylogeny, expression profiles and RNA interference (RNAi) of this gene in L. vannamei. We found that LvSRC contains two CCP domains and one MAM domain, with the highest expression level in the heart and relatively low expression level in other tissues. Notably, LvSRC exhibited significantly higher expression levels in the fast-growing group among groups with different growth rates, suggesting its potential involvement as a gene contributing to the growth of L. vannamei. RNAi of LvSRC inhibited body length and body weight gain compared to the control groups. Moreover, through RNA-seq analysis, we identified 598 differentially expressed genes (DEGs), including genes associated with growth, immunity, protein processing and modification, signal transduction, lipid synthesis and metabolism. Furthermore, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses revealed significant changes in the signaling pathways related to growth, lipid metabolism and immune response, suggesting that LvSRC exhibits the potential to participate in diverse physiological processes and immune regulation. These findings deepen our understanding of the structure and function of the SRC in shrimp and lay the foundation for further research into the regulatory mechanism of LvSRC. Additionally, they provide potential applications in shrimp genetics and breeding.

A pan-cancer characterization of immune-related NFIL3 identifies potential predictive biomarker.

Background: Nuclear factor interleukin 3 (NFIL3) mainly focuses on the regulation of the circadian rhythm and immune system. However, the potential role of NFIL3 in human cancers has not been studied extensively. Methods: We retrieved original data from the TCGA, TARGET, and GTEx datasets via the UCSC Xena browser (http://genome.ucsc.edu/) and integrated them using R version 3.6.4. NFIL3 expression was assessed using resources such as UCSC, GEPIA (http://gepia.cancer-pku.cn/), Kaplan-Meier Plotter (KM Plotter; https://kmplot.com/), and the Human Protein Atlas (HPA; https://www.proteinatlas.org/) databases. To investigate the prognostic implications of NFIL3, we utilized GEPIA, Kaplan-Meier Plotter, and PrognoScan (http://www.abren.net/PrognoScan/) datasets. For a comprehensive analysis across multiple cancer types, we employed pan-cancer data from UCSC, examining associations between NFIL3 expression and genomic heterogeneity, tumor mutational burden (TMB), microsatellite instability (MSI), tumor purity, and neoantigens. Furthermore, we explored the relationships between NFIL3 expression and the infiltration of immune cells and the expression of immune checkpoint genes. In the context of ovarian cancer, we validated the expression and functional relevance of NFIL3. Cell Counting Kit 8 (CCK8) assays were conducted to assess cell proliferation, while scratch and transwell assays were employed to evaluate cell migration capabilities. We further examined the interaction between NFIL3 and the p53 signaling pathway through quantitative real-time polymerase chain reaction (qRT-PCR), Western blot analysis, immunofluorescence confocal, and Coimmunoprecipitation (Co-IP) assays. Results: In general, NFIL3 expression in cancerous tissues exhibited diminished levels when compared to normal tissue samples. Notably, NFIL3 expression demonstrated a robust correlation with several pivotal aspects, including prognosis, immune cell infiltration, immune checkpoint-related genes, TMB, MSI, tumor purity, and the presence of neoantigens. Experimental investigations involving scratch assays, transwell assays, and assessments of cell proliferation in ovarian cancer cells have provided indications that NFIL3 may exert influence over cell migration and proliferation processes. Moreover, a substantial association between NFIL3 and the p53 signaling pathway was discerned through Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis, with subsequent validation through qRT-PCR, Western blot analysis, immunofluorescence confocal, and co-immunoprecipitation (Co-IP) assays. Conclusions: Therefore, we concluded NFIL3 may serve as a possible prognostic and immunological pan-cancer biomarker.

Fluorophore and nanozyme-functionalized DNA walking: A dual-mode DNA logic biocomputing platform for microRNA sensing in clinical samples.

Inspired by the programmability and modifiability of nucleic acids, point-of-care (POC) diagnostics for nucleic acid target detection is evolving to become more diversified and intelligent. In this study, we introduce a fluorescent and photothermal dual-mode logic biosensing platform that integrates catalytic hairpin assembly (CHA), toehold-mediated stand displacement reaction (SDR) and a DNA walking machine. Dual identification and signal reporting modules are incorporated into DNA circuits, orchestrated by an AND Boolean logic gate operator and magnetic beads (MBs). In the presence of bispecific microRNAs (miRNAs), the AND logic gate activates, driving the DNA walking machine, and facilitating the collection of hairpin DNA stands modified with FAM fluorescent group and CeO2@Au nanoparticles. The CeO2@Au nanoparticles, served as a nanozyme, can oxidize TMB into oxidation TMB (TMBox), enabling a near-infrared (NIR) laser-driven photothermal effect following the magnetic separation of MBs. This versatile platform was employed to differentiate between plasma samples from breast cancer patients, lung cancer patients, and healthy donors. The thermometer-readout transducers, derived from the CeO2@Au@DNA complexes, provided reliable results, further corroborated by fluorescence assays, enhancing the confidence in the diagnostics compared to singular detection method. The dual-mode logic biosensor can be easily customized to various nucleic acid biomarkers and other POC signal readout modalities by adjusting recognition sequences and modification strategies, heralding a promising future in the development of intelligent, flexible diagnostics for POC testing.

Ferroptosis: a new mechanism of traditional Chinese medicine for cancer treatment.

Ferroptosis, distinct from apoptosis, is a novel cellular death pathway characterized by the build-up of lipid peroxidation and reactive oxygen species (ROS) derived from lipids within cells. Recent studies demonstrated the efficacy of ferroptosis inducers in targeting malignant cells, thereby establishing a promising avenue for combating cancer. Traditional Chinese medicine (TCM) has a long history of use and is widely used in cancer treatment. TCM takes a holistic approach, viewing the patient as a system and utilizing herbal formulas to address complex diseases such as cancer. Recent TCM studies have elucidated the molecular mechanisms underlying ferroptosis induction during cancer treatment. These studies have identified numerous plant metabolites and derivatives that target multiple pathways and molecular targets. TCM can induce ferroptosis in tumor cells through various regulatory mechanisms, such as amino acid, iron, and lipid metabolism pathways, which may provide novel therapeutic strategies for apoptosis-resistant cancer treatment. TCM also influence anticancer immunotherapy via ferroptosis. This review comprehensively elucidates the molecular mechanisms underlying ferroptosis, highlights the pivotal regulatory genes involved in orchestrating this process, evaluates the advancements made in TCM research pertaining to ferroptosis, and provides theoretical insights into the induction of ferroptosis in tumors using botanical drugs.

Self-propelled assembly of nanoparticles with self-catalytic regulation for tumour-specific imaging and therapy.

Targeted assembly of nanoparticles in biological systems holds great promise for disease-specific imaging and therapy. However, the current manipulation of nanoparticle dynamics is primarily limited to organic pericyclic reactions, which necessitate the introduction of synthetic functional groups as bioorthogonal handles on the nanoparticles, leading to complex and laborious design processes. Here, we report the synthesis of tyrosine (Tyr)-modified peptides-capped iodine (I) doped CuS nanoparticles (CuS-I@P1 NPs) as self-catalytic building blocks that undergo self-propelled assembly inside tumour cells via Tyr-Tyr condensation reactions catalyzed by the nanoparticles themselves. Upon cellular internalization, the CuS-I@P1 NPs undergo furin-guided condensation reactions, leading to the formation of CuS-I nanoparticle assemblies through dityrosine bond. The tumour-specific furin-instructed intracellular assembly of CuS-I NPs exhibits activatable dual-modal imaging capability and enhanced photothermal effect, enabling highly efficient imaging and therapy of tumours. The robust nanoparticle self-catalysis-regulated in situ assembly, facilitated by natural handles, offers the advantages of convenient fabrication, high reaction specificity, and biocompatibility, representing a generalizable strategy for target-specific activatable biomedical imaging and therapy.