CD133-targeted multifunctional nanomicelles for dual-modality imaging and synergistic high-intensity focus ultrasound (HIFU) ablation on pancreatic cancer in nude mice.

Pancreatic cancer is an aggressive and highly fatal malignant tumor. Recent studies have shown that cancer stem cells (CSCs) play an important role in resisting current therapeutic modalities. Furthermore, CD133 is highly expressed in CSCs. High-intensity focused ultrasound (HIFU) is a promising non-invasive therapeutic strategy for unresectable pancreatic cancers. In our study, we synthesized targeted CD133 organosilane nanomicelles by encapsulating perfluorohexane (PFH). The CD133 antibody on the surface could specifically bind to CD133-positive pancreatic cancer cells and selectively concentrate in pancreatic cancer tumor tissues. PFH was introduced to improve the ablation effect of HIFU due to its liquid-gas phase transition properties. By combining with the dorsal skinfold window chamber model (DSWC) of pancreatic cancer in nude mice, multiphoton fluorescence microscopy was used to evaluate the targeting effect of nanomicelles on pancreatic cancer tumor tissue. These multifunctional nanomicelles synergistically affected HIFU treatment of pancreatic cancer, providing an integrated research platform for diagnosing and treating pancreatic cancer with HIFU.

Engineering Nanomedicine for Non-Viral RNA-Based Gene Therapy of Glioblastoma.

Glioblastoma multiforme (GBM) is the most common type of malignant tumor of the central nervous system, characterized by aggressiveness, genetic instability, heterogenesis, and unpredictable clinical behavior. Disappointing results from the current clinical therapeutic methods have fueled a search for new therapeutic targets and treatment modalities. GBM is characterized by various genetic alterations, and RNA-based gene therapy has raised particular attention in GBM therapy. Here, we review the recent advances in engineered non-viral nanocarriers for RNA drug delivery to treat GBM. Therapeutic strategies concerning the brain-targeted delivery of various RNA drugs involving siRNA, microRNA, mRNA, ASO, and short-length RNA and the therapeutical mechanisms of these drugs to tackle the challenges of chemo-/radiotherapy resistance, recurrence, and incurable stem cell-like tumor cells of GBM are herein outlined. We also highlight the progress, prospects, and remaining challenges of non-viral nanocarriers-mediated RNA-based gene therapy.

Sonogenetics-controlled synthetic designer cells for cancer therapy in tumor mouse models.

Bacteria-based therapies are powerful strategies for cancer therapy, yet their clinical application is limited by a lack of tunable genetic switches to safely regulate the local expression and release of therapeutic cargoes. Rapid advances in remote-control technologies have enabled precise control of biological processes in time and space. We developed therapeutically active engineered bacteria mediated by a sono-activatable integrated gene circuit based on the thermosensitive transcriptional repressor TlpA39. Through promoter engineering and ribosome binding site screening, we achieved ultrasound (US)-induced protein expression and secretion in engineered bacteria with minimal noise and high induction efficiency. Specifically, delivered either intratumorally or intravenously, engineered bacteria colonizing tumors suppressed tumor growth through US-irradiation-induced release of the apoptotic protein azurin and an immune checkpoint inhibitor, a nanobody targeting programmed death-ligand 1, in different tumor mouse models. Beyond developing safe and high-performance designer bacteria for tumor therapy, our study illustrates a sonogenetics-controlled therapeutic platform that can be harnessed for bacteria-based precision medicine.

Single-cell omics identifies inflammatory signaling as a trans-differentiation trigger in mouse embryos.

Trans-differentiation represents a direct lineage conversion; however, insufficient characterization of this process hinders its potential applications. Here, to explore a potential universal principal for trans-differentiation, we performed single-cell transcriptomic analysis of endothelial-to-hematopoietic transition (EHT), endothelial-to-mesenchymal transition, and epithelial-to-mesenchymal transition in mouse embryos. We applied three scoring indexes of entropies, cell-type signature transcription factor expression, and critical transition signals to show common features underpinning the fate plasticity of transition states. Cross-model comparison identified inflammatory-featured transition states and a common trigger role of interleukin-33 in promoting fate conversions. Multimodal profiling (integrative transcriptomic and chromatin accessibility analysis) demonstrated the inflammatory regulation of hematopoietic specification. Furthermore, multimodal omics and fate-mapping analyses showed that endothelium-specific Spi1, as an inflammatory effector, governs appropriate chromatin accessibility and transcriptional programs to safeguard EHT. Overall, our study employs single-cell omics to identify critical transition states/signals and the common trigger role of inflammatory signaling in developmental-stress-induced fate conversions.

Structure elucidation and anticancer activity of a heteropolysaccharide from white tea.

White tea, one of the six traditional teas in China, is made only through natural withering and low-temperature drying processes. It demonstrates diverse pharmacological and health-promoting effects, including antioxidant, antiviral, anticancer, and hypolipidemic activities. Despite the significance of polysaccharides in white tea leaves, their fine structure and physiological functions remain unexplored. In this study, the polysaccharide fragment WTP-80a with anticancer activity was isolated and purified from white tea through water extraction, alcohol precipitation, DEAE-52 ion exchange column chromatography, and sephacryl S-200 dextran gel column chromatography. WTP-80a exhibited a molecular weight of 1.14 × 105 Da and consisted of galactose (Gal), arabinose (Ara), rhamnose (Rha), and glucuronic acid (Glc-UA). The main chain skeleton of WTP-80a contained 3,6)-ß-Galp-(1→, 3)-α-Galp-(1→, 5)-α-Araf-(1 â†’ and 3)-α-Glcp-UA-(1→. Branch chains included α-Araf-(1 â†’ and ß-Rhap-(1 â†’ connected to the C3 and C6 positions of →3,6)-ß-Galp-(1→, respectively. In vitro anticancer experiments revealed that WTP-80a effectively hindered the proliferation, colony formation, migration, and invasion of B16F10 cells. Additionally, it induced apoptosis in B16F10 cells by blocking the G2/M phase, increasing active oxygen content, and reducing mitochondrial membrane potential. These findings provide a solid theoretical foundation for the application of white tea polysaccharides as anticancer products.

Release of extracellular vesicles triggered by low-intensity pulsed ultrasound: immediate and delayed reactions.

Previous studies have shown that ultrasound may stimulate the release of extracellular vesicles, improving the efficiency of tumor detection. However, it is unclear whether ultrasonic stimulation affects the distribution of extracellular vesicles, and the duration of such stimulation release has not been extensively studied. In this study, we stimulated cells with low-intensity pulsed ultrasound and used liposomes containing black hole quenchers to simulate natural extracellular vesicles, confirming that ultrasound has a destructive effect on vesicles and thus affects particle size distribution. Furthermore, we used proteomics technology to examine the protein expression profile of small vesicles and discovered that the expression of proteins involved in exosome biogenesis was down-regulated. We then looked into the regulation of the actin cytoskeleton and endocytosis pathways, which are required for intracellular vesicle transport, and discovered that ultrasound might induce F-actin depolymerization. The intracellular transport of the cation-independent mannose-6-phosphate receptor (CI-MPR) in the trans-Golgi network (TGN) and the amount of Rab7a protein were proportional to the culture time after LIPUS treatment.

Low-Intensity Pulsed Ultrasound Promotes the Repair of Achilles Tendinopathy by Downregulating the JAK/STAT Signaling Pathway in Rabbits.

Tendinopathy is a complex tendon injury or pathology outcome, potentially leading to permanent impairment. Low-intensity pulsed ultrasound (LIPUS) is emerging as a treatment modality for tendon disorders. However, the optimal treatment duration and its effect on tendons remain unclear. This study aims to investigate the efficacy of LIPUS in treating injured tendons, delineate the appropriate treatment duration, and elucidate the underlying treatment mechanisms through animal experiments. Ninety-six three-month-old New Zealand white rabbits were divided into normal control (NC) and model groups. The model group received Prostaglandin E2 (PGE2) injections to induce Achilles tendinopathy. They were then divided into model control (MC) and LIPUS treatment (LT) groups. LT received LIPUS intervention with a 1-MHz frequency, a pulse repetition frequency (PRF) of 1 kHz, and spatial average temporal average sound intensity ( [Formula: see text]) of 100 mW/cm2. MC underwent a sham ultrasound, and NC received no treatment. Assessments on 1, 4, 7, 14, and 28 days after LT included shear wave elastography (SWE), mechanical testing, histologic evaluation, ribonucleic acid sequencing (RNA-seq), polymerase chain reaction (PCR), and western blot (WB) analysis. SWE results showed that the shear modulus in the LT group was significantly higher than that in the MC group after LT for seven days. Histological results demonstrated improved tendon tissue alignment and fibroblast distribution after LT. Molecular analyses suggested that LIPUS may downregulate the Janus kinase/signal transducer and activator of transcription (JAK/STAT) signaling pathway and regulate inflammatory and matrix-related factors. We concluded that LT enhanced injured tendon elasticity and accelerated Achilles tendon healing. The study highlighted the JAK/STAT signaling pathway as a potential therapeutic target for LT of Achilles tendinopathy, guiding future research.

Combined Assessment of 2-D Ultrasound and Real-Time Shear Wave Elastography of Low-Intensity Pulsed Ultrasound Therapy Efficacy in Rabbits with Achilles Tendinopathy.

OBJECTIVE: Low-intensity pulsed ultrasound (LIPUS) has been gradually used to treat Achilles tendinopathy. However, there are limited non-invasive and efficient instruments for monitoring LIPUS efficacy in Achilles tendinopathy. The purpose of this study was to assess the therapeutic effectiveness of LIPUS after Achilles tendinopathy by 2-D ultrasound and real-time shear wave elastography (SWE). METHODS: Ninety New Zealand white rabbits were divided into control, sham and LIPUS groups after tendinopathy modeling. On days 1, 4, 7, 14 and 28, the Achilles tendon thickness and SWE Young's modulus on the long axis were measured. The tissues of the Achilles tendon were then evaluated histologically. RESULTS: The mean SWE values increased while the average thickness and histologic scores decreased, especially in the LIPUS group (9.5% and 80.7% on day 28, respectively). The SWE values in the LIPUS group were significantly lower than those in the control group on day 1 (121.0 kPa vs. 177.6 kPa) and peaked on day 7 (173.7 kPa, p < 0.001). By day 28, the SWE value had approached that of the control (191.2 kPa vs. 192.4 kPa), and had been significantly higher than that in the sham group since day 7. SWE values and histologic scores were correlated (r = -0.792, p < 0.01). The average thickness decreased in the three groups but did not differ significantly. CONCLUSION: Two-dimensional ultrasound is beneficial to the diagnosis of Achilles tendinopathy. SWE could quantify changes in Achilles tendon stiffness non-invasively during LIPUS treatment, enabling the study of early Achilles tendon healing after LIPUS treatment.

Optimizing surgical outcomes for elderly gallstone patients with a high body mass index using enhanced recovery after surgery protocol.

BACKGROUND: Rehabilitation of elderly patients with a high body mass index (BMI) after cholecystectomy carries risks and requires the adoption of effective perioperative management strategies. The enhanced recovery after surgery (ERAS) protocol is a comprehensive treatment approach that facilitates early patient recovery and reduces postoperative complications. AIM: To compare the effectiveness of traditional perioperative management methods with the ERAS protocol in elderly patients with gallbladder stones and a high BMI. METHODS: This retrospective cohort study examined data from 198 elderly patients with a high BMI who underwent cholecystectomy at the Shanghai Fourth People's Hospital from August 2019 to August 2022. Among them, 99 patients were managed using the traditional perioperative care approach (non-ERAS protocol), while the remaining 99 patients were managed using the ERAS protocol. Relevant indicator data were collected for patients preoperatively, intraoperatively, and postoperatively, and surgical outcomes were compared between the two groups. RESULTS: The comparison results between the two groups of patients in terms of age, sex, BMI, underlying diseases, surgical type, and preoperative hospital stay showed no statistically significant differences. However, the ERAS group had a significantly shorter preoperative fasting time than the non-ERAS group (4.0 ± 0.9 h vs 7.6 ± 0.9 h). Regarding intraoperative indicators, there were no significant differences between the two groups of patients. However, in terms of postoperative recovery, the ERAS protocol group exhibited significant advantages over the non-ERAS group, including a shorter hospital stay, lower postoperative pain scores and postoperative hunger scores, and higher satisfaction levels. The readmission rate was lower in the ERAS protocol group than in the non-ERAS group (3.0% vs 8.1%), although the difference was not significant. Furthermore, there were significant differences between the two groups in terms of postoperative nausea and vomiting severity, postoperative abdominal distention at 24 h, and daily life ability scores. CONCLUSION: The findings of this study demonstrate that the ERAS protocol confers significant advantages in postoperative outcomes following cholecystectomy, including reduced readmission rates, decreased postoperative nausea and vomiting, alleviated abdominal distension, and enhanced functional capacity. While the protocol may not exhibit significant improvement in early postoperative symptoms, it does exhibit advantages in long-term postoperative symptoms and recovery. These findings underscore the importance of implementing the ERAS protocol in the postoperative management of cholecystectomy patients, as it contributes to improving patients' recovery and quality of life while reducing health care resource utilization.

Polarized macrophages regulate fibro/adipogenic progenitor (FAP) adipogenesis through exosomes.

BACKGROUND: Macrophage polarization has been observed in the process of muscle injuries including rotator cuff (RC) muscle atrophy and fatty infiltration after large tendon tears. In our previous study, we showed that fibrogenesis and white adipogenesis of muscle residential fibro/adipogenic progenitors (FAPs) cause fibrosis and fatty infiltration and that brown/beige adipogenesis of FAPs promotes rotator cuff muscle regeneration. However, how polarized macrophages and their exosomes regulate FAP differentiation remains unknown. METHODS: We cultured FAPs with M0, M1, and M2 macrophages or 2 × 109 exosomes derived from M0, M1 and M2 with and without GW4869, an exosome inhibitor. In vivo, M0, M1, and M2 macrophages were transplanted or purified macrophage exosomes (M0, M1, M2) were injected into supraspinatus muscle (SS) after massive tendon tears in mice (n = 6). SS were harvested at six weeks after surgery to evaluate the level of muscle atrophy and fatty infiltration. RESULTS: Our results showed that M2 rather than M0 or M1 macrophages stimulates brown/beige fat differentiation of FAPs. However, the effect of GW4869, the exosome inhibitor, diminished this effect. M2 exosomes also promoted FAP Beige differentiation in vitro. The transplantation of M2 macrophages reduced supraspinatus muscle atrophy and fatty infiltration. In vivo injections of M2 exosomes significantly reduced muscle atrophy and fatty infiltration in supraspinatus muscle. CONCLUSION: Results from our study demonstrated that polarized macrophages directly regulated FAP differentiation through their exosomes and M2 macrophage-derived exosomes may serve as a novel treatment option for RC muscle atrophy and fatty infiltration.

The RNA-binding protein CSDE1 promotes hematopoietic stem and progenitor cell generation via translational control of Wnt signaling.

In vertebrates, the earliest hematopoietic stem and progenitor cells (HSPCs) are derived from a subset of specialized endothelial cells, hemogenic endothelial cells, in the aorta-gonad-mesonephros region through endothelial-to-hematopoietic transition. HSPC generation is efficiently and accurately regulated by a variety of factors and signals; however, the precise control of these signals remains incompletely understood. Post-transcriptional regulation is crucial for gene expression, as the transcripts are usually bound by RNA-binding proteins (RBPs) to regulate RNA metabolism. Here, we report that the RBP protein Csde1-mediated translational control is essential for HSPC generation during zebrafish early development. Genetic mutants and morphants demonstrated that depletion of csde1 impaired HSPC production in zebrafish embryos. Mechanistically, Csde1 regulates HSPC generation through modulating Wnt/ß-catenin signaling activity. We demonstrate that Csde1 binds to ctnnb1 mRNAs (encoding ß-catenin, an effector of Wnt signaling) and regulates translation but not stability of ctnnb1 mRNA, which further enhances ß-catenin protein level and Wnt signal transduction activities. Together, we identify Csde1 as an important post-transcriptional regulator and provide new insights into how Wnt/ß-catenin signaling is precisely regulated at the post-transcriptional level.

A near-infrared fluorescence-enhancing plasmonic biosensing microarray identifies soluble PD-L1 and ICAM-1 as predictive checkpoint biomarkers for cancer immunotherapy.

Sensitive and accurate biomarker-driven assay guidance has been widely adopted to identify responsive patients for immune checkpoint blockade (ICB) therapy to impede disease progression and extend survival. However, most current assays are invasive, requiring surgical pathology specimens and only informing monochronic information. Here, we report a multiplexed enhanced fluorescence microarray immunoassay (eFMIA) based on a nanostructured gold nanoisland substrate (AuNIS), which macroscopically amplifies near-infrared fluorescence (NIRF) of a structurally symmetric IRDye78 fluorophore by over two orders of magnitude of 202.6-fold. Aided by non-contact piezo-driven micro-dispensing (PDMD), eFMIA simultaneously and semi-quantitatively detected intracellular and secreted programmed death-ligand 1 (PD-L1) and intercellular adhesion molecule-1 (ICAM-1) in human nasopharyngeal carcinoma (NPC) cells. The assay performance was superior to fluorescence immunoassays (FIA) and enzyme-linked immunosorbent assays (ELISA), with lower detection limits. Using eFMIA, we found significantly differential levels of soluble PD-L1 (sPD-L1) and sICAM-1 in the sera of 28 cancer patients, with different clinical outcomes following anti-PD-1 ICB therapy. With a well-characterized mechanism, the high-performance plasmonic multiplexed assay with the composite biomarkers may be a valuable tool to assist clinicians with decision-making and patient stratification to afford predictive ICB therapy responses.

CD133-Targeted Hybrid Nanovesicles for Fluorescent/Ultrasonic Imaging-Guided HIFU Pancreatic Cancer Therapy.

Background: Pancreatic cancer is regarded as one of the most lethal types of tumor in the world, and optional way to treat the tumor are urgently needed. Cancer stem cells (CSCs) play a key role in the occurrence and development of pancreatic tumors. CD133 is a specific antigen for targeting the pancreatic CSCs subpopulation. Previous studies have shown that CSC-targeted therapy is effective in inhibiting tumorigenesis and transmission. However, CD133 targeted therapy combined with HIFU for pancreatic cancer is absent. Purpose: To improve therapeutic efficiency and minimize side effects, we carry a potent combination of CSCs antibody with synergist by an effective and visualized delivery nanocarrier to pancreatic cancer. Materials and Methods: Multifunctional CD133-targeted nanovesicles (CD133-grafted Cy5.5/PFOB@P-HVs) with encapsulated perfluorooctyl bromide (PFOB) in a 3-mercaptopropyltrimethoxysilane (MPTMS) shell modified with poly ethylene glycol (PEG) and superficially modified with CD133 and Cy 5.5 were constructed following the prescribed order. The nanovesicles were characterized for the biological and chemical characteristics feature. We explored the specific targeting capacity in vitro and the therapeutic effect in vivo. Results: The in vitro targeting experiment and in vivo FL and ultrasonic experiments showed the aggregation of CD133-grafted Cy5.5/PFOB@P-HVs around CSCs. In vivo FL imaging experiments demonstrated that the nanovesicles assemble for the highest concentration in the tumor at 24 h after administration. Under HIFU irradiation, the synergistic efficacy of the combination of the CD133-targeting carrier and HIFU for tumor treatment was obvious. Conclusion: CD133-grafted Cy5.5/PFOB@P-HVs combined with HIFU irradiation could enhance the tumor treatment effect not only by improving the delivery of nanovesicles but also by enhancing the HIFU thermal and mechanical effects in the tumor microenvironment, which is a highly effective targeted therapy for treating pancreatic cancer.

Systemic bevacizumab for pediatric patients with aggressive recurrent respiratory papillomatosis: One single-center experience of eight patients.

Recurrent respiratory papillomatosis (RRP) is a human papilloma virus (HPV)-driven benign neoplasm, affecting larynx, trachea, and even lung, leading to voice disorders, airway obstruction, and postobstructive pneumonia. Several case reports have documented the promising efficacy of intravenous bevacizumab in reducing the need for surgical intervention among RRP patients. Herein, we present our experience on systemic bevacizumab for pediatric patients with aggressive RRP. Methods: We retrospectively analyzed clinical, laboratory, radiological, and bronchoscopy findings of pediatric patients with aggressive RRP treated with systemic bevacizumab from July 26, 2021 to March 1, 2022. Results: Eight consecutive patients were included. Median age at treatment initiation was 5.5 (range 2.5-8) years old. Twenty-five percentage (2/8) of patients experienced tracheotomy. Pulmonary papilloma was present in 62.5% (5/8) patients. Patients received median 10 cycles of bevacizumab (range 5-12). Patients received initial dosing of 4-7.5 mg/kg every 2-10 weeks of bevacizumab and subsequently extended after achieving the maximum response. None of the patients required surgical intervention during a median 10 (range 8.2-15.4) months follow-up after initiating bevacizumab treatment. Both patients with evaluable lung lesions showed objective response. Only Grade 1 abdominal pain and Grade 1 hyperuricemia were recorded. Conclusion: Systemic bevacizumab seems to be a well-tolerated and effective treatment option for pediatric patients with aggressive RRP.

Activation of lineage competence in hemogenic endothelium precedes the formation of hematopoietic stem cell heterogeneity.

Hematopoietic stem and progenitor cells (HSPCs) are considered as a heterogeneous population, but precisely when, where and how HSPC heterogeneity arises remain largely unclear. Here, using a combination of single-cell multi-omics, lineage tracing and functional assays, we show that embryonic HSPCs originate from heterogeneous hemogenic endothelial cells (HECs) during zebrafish embryogenesis. Integrated single-cell transcriptome and chromatin accessibility analysis demonstrates transcriptional heterogeneity and regulatory programs that prime lymphoid/myeloid fates at the HEC level. Importantly, spi2+ HECs give rise to lymphoid/myeloid-primed HSPCs (L/M-HSPCs) and display a stress-responsive function under acute inflammation. Moreover, we uncover that Spi2 is required for the formation of L/M-HSPCs through tightly controlling the endothelial-to-hematopoietic transition program. Finally, single-cell transcriptional comparison of zebrafish and human HECs and human induced pluripotent stem cell-based hematopoietic differentiation results support the evolutionary conservation of L/M-HECs and a conserved role of SPI1 (spi2 homolog in mammals) in humans. These results unveil the lineage origin, biological function and molecular determinant of HSPC heterogeneity and lay the foundation for new strategies for induction of transplantable lineage-primed HSPCs in vitro.

Efficacy and safety of angiogenesis inhibitors plus immune checkpoint inhibitors in advanced soft tissue sarcoma: a real-world, single-center study.

Angiogenesis inhibitors (AIs) and immune checkpoint inhibitors (ICIs) are new treatment options for advanced soft tissue sarcoma (STS) patients. This study evaluated the efficacy and safety of AIs plus ICIs in patients with advanced STS. A retrospective cohort study was performed on STS patients treated with AIs and ICIs at Shandong Cancer Hospital and Institute between August 2020 and December 2021. The primary endpoint was objective response rate (ORR); secondary endpoints included progression-free survival (PFS), disease control rate (DCR), overall survival (OS), and adverse events. Thirty-three patients were enrolled; 27 were evaluable for objective response. The ORR and DCR were 48.1% (95% CI 30.7-66.0%) and 85.2% (95% CI 67.5-94.1%). With a median follow-up of 7.6 months (range, 0.8-25.5), the median PFS for all 33 patients was 8.90 months (95% CI 5.98-11.82). The median OS was not reached. The most common treatment-related adverse events (TRAEs) of any grade were hypertension (50.0%), ECG T-wave abnormality (30.0%), hypothyroidism (26.7%), elevated alanine aminotransferase or aspartate aminotransferase (23.3%), elevated thyroid-stimulating hormone (23.3%), and fatigue (16.7%). The most common grade 3-4 TRAE was hypertension (27.3%). Three serious TRAEs (two myocarditis and one rapid atrial fibrillation) were recorded. This study suggests that adding AIs to ICIs is beneficial in STS.

H2/D2 separation in gas chromatography through a MOF-on-MOF strategy using γ-AlOOH@Al(OH)(1,4-NDC)@ZIF-67 as the stationary phase via additive effects of chemical affinity quantum sieving and kinetic sieving.

The reaction of porous γ-Al2O3 particles acting as both a sacrificial template and an aluminum source with 1,4-naphthalene diacid (H2NDC) resulted in the formation of γ-AlOOH@Al(OH)(1,4-NDC) composites, in which ZIF-67 was then loaded by the in situ crystallization method, leading to the formation of γ-AlOOH@Al(OH)(1,4-NDC)@ZIF-67 composites. The deliberately designed composite was used to separate H2/D2 at 77 K in a 1 m chromatographic column. The results demonstrated that the optimized composite can achieve the effective separation of H2/D2 in gas chromatography due to the additive effects of kinetic sieving and chemical affinity quantum sieving of Al(OH)(1,4-NDC) and ZIF-67. By optimizing chromatographic separation conditions, the resolution R reached 2.02 with the separation time t = 7.72 min. The composite also showed satisfactory repeatability and reproducibility.

Rational design of near-infrared ratiometric fluorescent probes for real-time tracking of ß-galactosidase in vivo.

ß-Galactosidase (ß-gal) is a hydrolytic enzyme in lysosomes and is also an important biomarker of cellular senescence and primary ovarian cancer. Therefore, real-time non-invasive detection of ß-gal activity in vivo is of great significance for the prevention of cell senescence and early diagnosis of ovarian cancer. We designed an enzyme-activated proportional near-infrared (NIR) probe (Gal-Br-NO2) for real-time fluorescence quantification and capture of ß-gal activity in vivo. The main characteristics of the Gal-Br-NO2 probe include short response time (less than 10 min), large Stokes displacement (155 nm), and near-infrared fluorescence emission (670 nm). The probe has also been successfully used to detect ß-gal in ovarian cancer cells and senile cells and can accurately detect endogenous ß-gal in zebrafish. Our work provides a potential tool for pre-clinical real-time tracking of ß-gal activity in vivo and early diagnosis of disease.

Integrative analysis of platelet-related genes for the prognosis of esophageal cancer.

BACKGROUND: Every year, esophageal cancer is responsible for 509000 deaths and around 572000 new cases worldwide. Although esophageal cancer treatment options have advanced, patients still have a dismal 5-year survival rate. AIM: To investigate the relationship between genes associated to platelets and the prognosis of esophageal cancer. METHODS: We searched differentially expressed genes for changes between 151 tumor tissues and 653 normal, healthy tissues using the "limma" package. To develop a prediction model of platelet-related genes, a univariate Cox regression analysis and least absolute shrinkage and selection operator Cox regression analysis were carried out. Based on a median risk score, patients were divided into high-risk and low-risk categories. A nomogram was created to predict the 1-, 2-, and 3-year overall survival (OS) of esophageal cancer patients using four platelet-related gene signatures, TNM stages, and pathological type. Additionally, the concordance index, receiver operating characteristic curve, and calibration curve were used to validate the nomogram. RESULTS: The prognosis of esophageal cancer was associated to APOOL, EP300, PLA2G6, and VAMP7 according to univariate Cox regression analysis and least absolute shrinkage and selection operator regression analysis. Patients with esophageal cancer at high risk had substantially shorter OS than those with cancer at low risk, according to a Kaplan-Meier analysis (P < 0.05). TNM stage (hazard ratio: 2.187, 95% confidence interval: 1.242-3.852, P = 0.007) in both univariate and multivariate Cox regression and risk score were independently correlated with OS (hazard ratio: 2.451, 95% confidence interval: 1.599-3.756, P < 0.001). CONCLUSION: A survival risk score model and independent prognostic variables for esophageal cancer have been developed using APOOL, EP300, PLA2G6, and VAMP7. OS for esophageal cancer might be predicted using the nomogram based on TNM stage, pathological type, and risk score. The nomogram demonstrated strong predictive ability, as shown by the concordance index, receiver operating characteristic curve, and calibration curve.

Comprehensive analysis of the relationship between cuproptosis-related genes and esophageal cancer prognosis.

BACKGROUND: Esophageal cancer is one of the most common malignant tumors of the digestive system, with a 5-year survival rate of 15% to 50%. Cuproptosis, a unique kind of cell death driven by protein lipoylation, is strongly connected to mitochondrial metabolism. The clinical implications of cuproptosis-related genes in esophageal cancer, however, are mainly unknown. AIM: To identify cuprotosis-related genes that are differentially expressed in esophageal cancer and investigate their prognostic significance. METHODS: With |log fold change| > 1 and false discovery rate < 0.05 as criteria, the Wilcox test was used to evaluate the differentially expressed genes between 151 tumor tissues and 151 normal esophageal tissues. Cuproptosis-related genes were selected to be linked with prognosis using univariate Cox regression analysis. Genes were separated into high- and low- expression groups based on their cutoff value of gene expression, and the correlation between the two groups and overall survival or progression-free survival was investigated using the log-rank test. The C-index, calibration curve, and receiver operator characteristic (ROC) curve were used to assess a nomogram containing clinicopathological characteristics and cuproptosis-related genes. RESULTS: Pyruvate dehydrogenase A1 (PDHA1) was found to be highly correlated with prognosis in univariate Cox regression analysis (hazard ratio = 22.96, 95% confidence interval = 3.09-170.73; P = 0.002). According to Kaplan-Meier survival curves, low expression of PDHA1 was associated with a better prognosis (log-rank P = 0.0007). There was no significant correlation between PDHA1 expression and 22 different types of immune cells. Tumor necrosis factor superfamily member 15 (TNFSF15) (P = 3.2 × 10-6; r = 0.37), TNFRSF14 (P = 8.1 × 10-8; r = 0.42), H long terminal repeat-associating 2 (P = 6.0 × 10-8; r = 0.42) and galectin 9 (P = 3.1 × 10-6; r = 0.37) were all found to be considerably greater in the high PDHA1 expression group, according to an analysis of genes related to 47 immunological checkpoints. The low PDHA1 expression group had significantly lower levels of cluster of differentiation 44 (CD44) (P = 0.00028; R = -0.29), TNFRSF18 (P = 1.2 × 10-5; R = -0.35), programmed cell death 1 ligand 2 (P = 0.0032; R = -0.24), CD86 (P = 0.018; R = -0.19), and CD40 (P = 0.0047; R = -0.23), and the differences were statistically significant. We constructed a prognostic nomogram incorporating pathological type, tumor-node-metastasis stage, and PDHA1 expression, and the C-index, calibration curve, and ROC curve revealed that the nomogram's predictive performance was good. CONCLUSION: Cuproptosis-related genes can be used as a prognostic predictor for esophageal cancer patients, providing novel insights into cancer treatment.