Development of a Serum-Based MicroRNA Signature for Early Detection of Pancreatic Cancer: A Multicenter Cohort Study.

BACKGROUND: A grim prognosis of pancreatic cancer (PCa) was attributed to the difficulty in early diagnosis of the disease. AIMS: Identifying novel biomarkers for early detection of PCa is thus urgent to improve the overall survival rates of patients. METHODS: The study was performed firstly by identification of candidate microRNAs (miRNAs) in formalin-fixed, paraffin-embedded tissues using microarray profiles, and followed by validation in a serum-based cohort study to assess clinical utility of the candidates. In the cohorts, a total of 1273 participants from four centers were retrospectively recruited as two cohorts including training and validation cohort. The collected serum specimens were analyzed by real-time polymerase chain reaction. RESULTS: We identified 27 miRNAs expressed differentially in PCa tissues as compared to the benign. Of which, the top-four was selected as a panel whose diagnostic efficacy was fully assessed in the serum specimens. The panel exhibited superior to CA19-9, CA125, CEA and CA242 in discriminating patients with early stage PCa from healthy controls or non-PCa including chronic pancreatitis as well as pancreatic cystic neoplasms, with the area under the curves (AUC) of 0.971 (95% CI 0.956-0.987) and 0.924 (95% CI 0.899-0.949), respectively. Moreover, the panel eliminated interference from other digestive tumors with a specificity of 90.2%. CONCLUSIONS: A panel of four serum miRNAs was developed showing remarkably discriminative ability of early stage PCa from either healthy controls or other pancreatic diseases, suggesting it may be developed as a novel, noninvasive approach for early screening of PCa in clinic.

ITGAV Promotes the Progression of Head and Neck Squamous Cell Carcinoma.

Head and neck squamous cell carcinoma (HNSCC) refers to the malignancy of squamous cells in the head and neck region. Ranked as the seventh most common cancer worldwide, HNSCC has a very low survival rate, highlighting the importance of finding therapeutic targets for the disease. Integrins are cell surface receptors that play a crucial role in mediating cellular interactions with the extracellular matrix (ECM). Within this protein family, Integrin αV (ITGAV) has received attention for its important functional role in cancer progression. In this study, we first demonstrated the upregulation of ITGAV expression in HNSCC, with higher ITGAV expression levels correlating with significantly lower overall survival, based on TCGA (the Cancer Genome Atlas) and GEO datasets. Subsequent in vitro analyses revealed an overexpression of ITGAV in highly invasive HNSCC cell lines UM1 and UMSCC-5 in comparison to low invasive HNSCC cell lines UM2 and UMSCC-6. In addition, knockdown of ITGAV significantly inhibited the migration, invasion, viability, and colony formation of HNSCC cells. In addition, chromatin immunoprecipitation (ChIP) assays indicated that SOX11 bound to the promoter of ITGAV gene, and SOX11 knockdown resulted in decreased ITGAV expression in HNSCC cells. In conclusion, our studies suggest that ITGAV promotes the progression of HNSCC cells and may be regulated by SOX11 in HNSCC cells.

Treatment of post-traumatic complete bony ankylosed elbow using total arthroplasty and hernia patch - A case report.

INTRODUCTION AND IMPORTANCE: The elbow is one of the most mobile joints, and its movement is very important. Bony ankylosed elbow is an uncommon condition leading to complete loss of activity of elbow, and then lead to severe disability and limitation in activities of daily living. CASE PRESENTATION: A 63-year-old woman sustained comminuted fracture of left distal humerus. She underwent open reduction and internal fixation by plates. After the plates were removed in 2016，stiffness developed.The elbow was stable but fixed at 90°ï¼Œthere was no vascular injury or deficit in sensory and motor function of the ulnar nerve. She hopes to eliminate pain and restore normal mobility compatible with ADL. CLINICAL DISCUSSION: Complete bony ankylosis of the elbow joint may be caused by trauma, rheumatic disease, burns, congenital stiffness and other conditions. Even with the compensation of shoulder and wrist, it will still have a great impact on upper limb function. Whether to treat mainly depends on whether the patient has the require to improve the functionality and return to daily activities. Treatment methods are very limited, including interposition arthroplasty and TEA. Defect of soft tissue appeared was seen in our case, Hernia Patch was innovatively applied to reconstruct the defect of soft tissue and maintain continuity of elbow extension mechanism. CONCLUSION: Patients with post-traumatic elbow joint ankylosis were suffered from severe bony abnormalities, but also soft tissue contracture or defects due to multiple operations and trauma. We present a case of complete bony ankylosed elbow treated with total elbow arthroplasty and Hernia Patch.

Oriented Ultrathin π-complexation MOF Membrane for Ethylene/Ethane and Flue Gas Separations.

Rational design and engineering of high-performance molecular sieve membranes towards C2 H4 /C2 H6 and flue gas separations remain a grand challenge to date. In this study, through combining pore micro-environment engineering with meso-structure manipulation, highly c-oriented sub-100 nm-thick Cu@NH2 -MIL-125 membrane was successfully prepared. Coordinatively unsaturated Cu ions immobilized in the NH2 -MIL-125 framework enabled high-affinity π-complexation interactions with C2 H4 , resulting in an C2 H4 /C2 H6 selectivity approaching 13.6, which was 9.4 times higher than that of pristine NH2 -MIL-125 membrane; moreover, benefiting from π-complexation interactions between CO2 and Cu(I) sites, our membrane displayed superior CO2 /N2 selectivity of 43.2 with CO2 permeance of 696 GPU, which far surpassed the benchmark of other pure MOF membranes. The above multi-scale structure optimization strategy is anticipated to present opportunities for significantly enhancing the separation performance of diverse molecular sieve membranes.

Single-Cell Analysis of circRNA Using ddPCR.

Droplet digital polymerase chain reaction (ddPCR) is a new quantitative PCR method based on water-oil emulsion droplet technology. ddPCR enables highly sensitive and accurate quantification of nucleic acid molecules, especially when their copy numbers are low. In ddPCR, a sample is fractionated into ~20,000 droplets, and every nanoliter-sized droplet undergoes PCR amplification of the target molecule. The fluorescence signals of droplets are then recorded by an automated droplet reader. Circular RNAs (circRNAs) are single-stranded, covalently closed RNA molecules that are ubiquitously expressed in animals and plants. CircRNAs are promising as biomarkers for cancer diagnosis and prognosis and as therapeutic targets or agents to inhibit oncogenic microRNAs or proteins (Kristensen LS, Jakobsen T, Hager H, Kjems J, Nat Rev Clin Oncol 19:188-206, 2022). In this chapter, the procedures for the quantitation of a circRNA in single pancreatic cancer cells using ddPCR are described.

A self-amplified ferroptosis nanoagent that inhibits the tumor upstream glutathione synthesis to reverse cancer chemoresistance.

Ferroptosis has recently become an attractive strategy to combat the chemoresistance of cancer cells, but the intracellular ferroptosis defense system greatly challenges the efficient ferroptosis induction. Herein, we report a ferrous metal-organic framework-based nanoagent (FMN) that inhibits the intracellular upstream glutathione synthesis and induces self-amplified ferroptosis of cancer cells, for reversing chemoresistance and boosting chemotherapy. The FMN is loaded with SLC7A11 siRNA (siSLC7A11) and chemotherapeutic doxorubicin (DOX), which shows enhanced tumor cell uptake and retention, thus ensuring the effective DOX delivery and tumor intracellular iron accumulation. Importantly, the FMN simultaneously catalyzes the iron-dependent Fenton reaction and triggers the siSLC7A11-mediated suppression of upstream glutathione synthesis for intracellularly self-amplified ferroptosis, which further inhibits P-glycoprotein activity for DOX retention, and regulates the expression of Bcl-2/Bax to reverse the apoptotic resistance state of tumor cells. The FMN-mediated ferroptosis is also demonstrated in ex vivo patient-derived tumor fragment platform. Consequently, FMN successfully reverses cancer chemoresistance and achieves a highly efficient in vivo therapeutic efficacy in MCF7/ADR tumor-bearing mice. Our study provides a self-amplified ferroptosis strategy via inhibiting intracellular upstream glutathione synthesis, which is effective to reverse cancer chemoresistance.

Ferric-loaded lipid nanoparticles inducing ferroptosis-like cell death for antibacterial wound healing.

Skin infection is a major health issue that usually is caused by the continuous proliferation of bacteria in wounds. With the abuse of antibiotics worldwide, the battle against skin infection is becoming more and more difficult. Therefore, the development of new ways with different antibacterial mechanisms to current antibiotics is urgently needed. Inspired by the powerful inhibition of ferroptosis used in cancer therapy, here in our study, ferric-loaded lipid nanoparticles (Fe-LNPs) with unform size (∼130 nm) and surface charge (∼12 mV) were constructed and found to effectively inhibit the growth of both Gram positive (Staphylococcus aureus, S. aureus) and negative (Escherichia coli, E. coli) strains, possibly due to induction of ferroptosis-like cell death mechanisms. Most importantly, Fe-LNPs can also effectively inhibit the proliferation of S. aureus in a skin infection model and promote the healing of wounds. The Fe-LNPs can be applied as a powerful antibacterial formulation for future application in clinic.

Efficacy of electroacupuncture combined with intravenous patient-controlled analgesia after cesarean delivery: a randomized clinical trial.

BACKGROUND: Electroacupuncture is a nonpharmacologic intervention for analgesia that is widely recognized as therapy for pain. However, the clinical efficacy of electroacupuncture combined with patient-controlled intravenous analgesia for postoperative analgesia after cesarean delivery remains unclear. OBJECTIVE: This study aimed to assess the efficacy of electroacupuncture + patient-controlled intravenous analgesia for postoperative analgesia after cesarean delivery, determine the optimal frequency for the best analgesic effect, and explore the underlying mechanism of action. STUDY DESIGN: This single-center, randomized, single-blinded, sham acupuncture controlled clinical trial was conducted at a tertiary university hospital in China. Female patients who underwent cesarean delivery and received fentanyl as patient-controlled intravenous analgesia for postoperative analgesia were enrolled. Patients were after surgery randomized to receive 2 Hz electroacupuncture treatment (n=53), 20/100 Hz electroacupuncture treatment (n=53), or sham electroacupuncture treatment (n=52) (controls). The 2 electroacupuncture groups received electroacupuncture treatment at 2 or 20/100 Hz at the ST36 and SP6 points, whereas, in the sham electroacupuncture group, sham electroacupuncture was performed at nonmeridian points with nonenergized electroacupuncture instruments. Of note, 4 electroacupuncture treatments were performed in all groups at 6, 12, 24, and 48 hours after surgery. The primary outcome was the number of analgesic pump compressions at 48 hours after surgery. The secondary outcomes included number of analgesic pump compressions at 6, 12, and 24 hours after surgery; pain scores at 6, 12, 24, and 48 hours after surgery; fentanyl consumption at 48 hours after surgery; interleukin 6 and procalcitonin levels at 12 and 48 hours after surgery; and time to first exhaust. RESULTS: Overall, 174 primigravida women were included in the intention-to-treat analysis. The number of analgesic pump compressions and pain scores at all 4 time points and fentanyl consumption at 48 hours after surgery were significantly lower in the electroacupuncture treatment groups than in the sham electroacupuncture group (P<.001). CONCLUSION: Electroacupuncture + patient-controlled intravenous analgesia had a significantly better analgesic effect than sham electroacupuncture + patient-controlled intravenous analgesia within 48 hours after surgery. Thus, electroacupuncture can be considered safe and effective and may improve the efficacy of patient-controlled intravenous analgesia for pain management after cesarean delivery. Electroacupuncture can be recommended as a routine complementary therapy for pain control after cesarean delivery.

In-Depth Metaproteomics Analysis of Oral Microbiome for Lung Cancer.

The human oral microbiome correlates with numerous diseases, including lung cancer. Identifying the functional changes by metaproteomics helps understand the disease-related dysbiosis, yet characterizing low-abundant bacteria is challenging. Here, we developed a free-flow isoelectric focusing electrophoresis-mass spectrometry- (FFIEF-MS-) based metaproteomics strategy to reduce host interferences and enrich low-abundant bacteria for in-depth interpretation of the oral microbiome. With our method, the number of interfering peptides decreased by 52.87%, whereas the bacterial peptides and species increased by 94.97% and 44.90%, respectively, compared to the conventional metaproteomics approach. We identified 3647 bacterial proteins, which is the most comprehensive oral metaproteomics study to date. Lung cancer-associated bacteria were validated among an independent cohort. The imbalanced Fusobacterium nucleatum and Prevotella histicola and their dysregulated functions in inhibiting immune response and maintaining cell redox homeostasis were revealed. The FFIEF-MS may serve as a valuable strategy to study the mechanisms between human diseases and microbiomes with broader applications.

Risk Factors Involved in the Early and Medium-Term Poor Outcomes of Percutaneous Endoscopic Transforaminal Discectomy: A Single-Center Experience.

Objective: To investigate the risk factors involved in the early and medium-term poor outcomes of percutaneous endoscopic transforaminal discectomy (PETD) treatment of lumbar disc herniation (LDH) at the L4-5 level. Methods: Between January 2015 and May 2020, we recruited 148 LDH patients at the L4-5 level who underwent PETD surgery. The patients were divided into Groups A and B, according to the surgical outcomes. Good and excellent outcomes were categorized into Group A, and generally good and poor outcomes were categorized into Group B. Clinical parameters (age, gender, symptom duration, hospital stay, operation time, blood loss, straight-leg raising (SLR), visual analog scale (VAS), Oswestry Disability Index (ODI) score and modified MacNab criteria) and radiologic parameters (foraminal height (FH), intervertebral height index (IHI), intervertebral angle (IVA), sagittal range of motion (sROM), and lumbar lordosis (LL)) were collected and analyzed using univariate and multiple logistic regression analyses. Results: At the 6-month follow-up post operation, univariate analysis revealed that the symptom duration, SLR, IHI, and sROM were strongly associated with poor outcomes. However, multiple logistic regression analysis demonstrated that prolonged symptom duration, large SLR angel, and large sROM were independent risk factors for poor outcomes. At the 2-year follow-up post operation, univariate analysis suggested that advanced age, prolonged symptom duration, large preoperative VAS score, small FH, small IHI, and large sROM were potential risk factors for poor outcomes. However, multiple logistic regression analysis demonstrated that prolonged symptom duration, small IHI, and large sROM were independent risk factors for poor outcomes. Conclusion: Our study demonstrated that prolonged symptom duration, large SLR angel, and large sROM were independent risk factors for poor outcomes immediately following PETD at the L4-5 level. However, prolonged symptom duration, small IHI, and large sROM were independent risk factors for poor outcomes at medium-term post PETD at the L4-5 level.

Dynamic ginsenoside-sheltered nanocatalysts for safe ferroptosis-apoptosis combined therapy.

Chemodynamic therapy (CDT)-activated apoptosis is a potential anticancer strategy. However, CDT encounters a bottleneck in clinical translation due to its serious side effects and low efficacy. Here, we first reveal that surface engineering of ginsenoside Rg3 dramatically alters the organ distribution and tumor enrichment of systematically administered nanocatalysts using the orthotopic pancreatic tumor model while avoiding toxicity and increasing efficacy in vivo to address the key and universal toxicity problems encountered in nanomedicine. Compared with nanocatalysts alone, Rg3-sheltered dynamic nanocatalysts form hydrophilic nanoclusters, prolonging their circulation lifespan in the blood, protecting the internal nanocatalysts from leakage while allowing their specific release at the tumor site. Moreover, the nanoclusters provide a drug-loading platform for Rg3 so that more Rg3 reaches the tumor site to achieve obvious synergistic effect with nanocatalysts. Rg3-sheltered dynamic nanocatalysts can simultaneously activate ferroptosis and apoptosis to significantly improve anticancer efficacy. Systematic administration of ginsenoside Rg3-sheltered nanocatalysts inhibited 86.6% of tumor growth without toxicity and prolonged the survival time of mice. This study provides a promising approach of nanomedicine with high biosafety and a new outlook for catalytic ferroptosis-apoptosis combined antitumor therapies. STATEMENT OF SIGNIFICANCE: Chemodynamic therapy (CDT) has limited clinical efficacy in cancer. In this study, we developed Rg3-sheltered dynamic nanocatalysts, which could simultaneously activate ferroptosis based on CDT-activated apoptosis, and ultimately form a combined therapy of ferroptosis-apoptosis to kill tumors. Studies have shown that the nanocatalysts after Rg3 surface engineering dramatically alters the pharmacokinetics and organ distribution of the nanocatalysts after being systematically administered, resulting in avoiding the toxicity of the nanocatalysts. Nanocatalysts also act as a drug-loading platform, guiding more Rg3 into the tumor site. This study emphasizes that nanocatalysts after Rg3 surface engineering improve the safety and effectiveness of ferroptosis-apoptosis combined therapy, providing an effective idea for clinical practices.

A K+-sensitive AND-gate dual-mode probe for simultaneous tumor imaging and malignancy identification.

Although molecular imaging probes have the potential to non-invasively diagnose a tumor, imaging probes that can detect a tumor and simultaneously identify tumor malignancy remain elusive. Here, we demonstrate a potassium ion (K+) sensitive dual-mode nanoprobe (KDMN) for non-invasive tumor imaging and malignancy identification, which operates via a cascaded 'AND' logic gate controlled by inputs of magnetic resonance imaging (MRI) and fluorescence imaging (FI) signals. We encapsulate commercial K+ indicators into the hollow cavities of magnetic mesoporous silica nanoparticles, which are subsequently coated with a K+-selective membrane that exclusively permits the passage of K+ while excluding other cations. The KDMN can readily accumulate in tumors and enhance the MRI contrast after systemic administration. Spatial information of the tumor lesion is thus accessible via MRI and forms the first layer of the 'AND' gate. Meanwhile, the KDMN selectively captures K+ and prevents interference from other cations, triggering a K+-activated FI signal as the second layer of the 'AND' gate in the case of a malignant tumor with a high extracellular K+ level. This dual-mode imaging approach effectively eliminates false positive or negative diagnostic results and allows for non-invasive imaging of tumor malignancy with high sensitivity and accuracy.

PVT1 promotes resistance to 5-FU in colon cancer via the miR-486-5p/CDK4 axis.

Drug resistance in tumors is a major issue, limiting the curative efficacy of currently available cancer chemotherapeutics. 5-Fluorouracil (5-FU) is a commonly applied therapeutic drug in colon cancer patient regimens; however, the majority of patients develop resistance to 5-FU in the later stages of the disease, rendering this chemotherapy ineffective. Drug resistance is the main factor underlying the poor prognosis of patients with colon cancer. In recent years, a number of studies have confirmed that long non-coding (lnc)RNAs may play vital roles in tumor resistance. In the present study, the Gene Expression Omnibus (GEO) and lncRNADisease2 databases were screened for colon cancer-associated expression patterns of lncRNA plasmacytoma variant translocation 1 (PVT1). Subsequently, reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was used to detect changes in PVT1 expression in resistant cell lines, and a Cell Counting Kit-8 (CCK-8) assay kit was used to assess the effects of PVT1 knockdown on the half maximal inhibitory concentrations of parental and 5-FU-resistant HCT116 cells. Subsequently, CCK-8, clone formation, and flow cytometric assays were performed to investigate the effects of PVT1 knockdown on the sensitivity of HCT116-5FU-resistant cells to 5-FU. Dual-luciferase assay, RNA pull-down and RNA immunoprecipitation assays verified the interactive regulation of PVT1, miR-486-5p and cyclin dependent kinase 4 (CDK4). PVT1 was highly expressed in HCT116-5FU-resistant cells, as compared to its expression in HCT116 parental cells. PVT1 knockdown significantly reduced the resistance of HCT116-5FU-resistant cells to 5-FU. In addition, PVT1 upregulated CDK4 expression by adsorbing miR-486-5p; however, CDK4 overexpression restored the effects of miR-486-5p inhibition on HCT116-5-FU-resistant cells. Additionally, PVT1 knockdown partially rescued CDK4 overexpression in HCT116-5-FU-resistant cells. On the whole, the findings of the present study suggest that PVT1 promotes the resistance of colon cancer cells to 5-FU by regulating the miR-486-5p/CDK4 axis. Therefore, PVT1 may prove to be a potential target for counteracting resistance to 5-FU in colon cancer therapy.

A wearable gamma radiation-responsive granulocyte colony-stimulating factor microneedle system protecting against ionizing radiation-induced injury.

Exposure to a nuclear accident or a radiological attack may cause serious death events due to ionizing radiation-induced injury and acute radiation syndrome (ARS). Recombinant human granulocyte colony-stimulating factor (G-CSF) is now used for the treatment of ARS. However, the current injection formulation might not ensure treatment as early as possible after a nuclear accident, resulting in a decrease in therapeutic efficiency. In the present study, we have developed a G-CSF wearable system (GWS) consisting of a commercial microchip, a temperature sensor, a gamma-ray detection sensor, a flexible heater, and a G-CSF temperature-sensitive microneedle (GTSMN) patch. G-CSF-containing hyaluronic acid solutions were cast into the mold to obtain G-CSF microneedles (GMNs), which were coated with a temperature-sensitive layer of dodecanoic acid-cetylamine salt to obtain GTSMNs. The flexible heater was prepared by jet printing Ag nanoparticle inks. The GWS and its components are explored and optimized in the aspects of electronics, mechanics, heat transfer and drug diffusion. The γ radiation signal is sensitively monitored by the GWS. The wearable G-CSF system immediately releases G-CSF into the body in response to signal feedback and provides maximal protection against ionizing radiation-induced injury. Therefore, the GWS is a promising wearable system against emergent ionizing radiation injury. STATEMENT OF SIGNIFICANCE: Ionizing radiation-induced injury is always the very important public health problem all the global people care. Some medicines have been applied to protect the body from the injury. Unfortunately, sometimes the injuries accidently happen and the medicines cannot be administered in time, leading to serious acute radiation syndrome. Here, we design a wearable system loading G-CSF that has been approved by FDA to protect the body from ionizing radiation-induced injury. This system consists of a commercial microchip, a temperature sensor, a Gamma-ray detection sensor, a flexible heater, and a G-CSF temperature-sensitive microneedle patch. It can monitor γ radiation and immediately release G-CSF into the body to protect the body to the maximal extent. Therefore, the system is a promising wearable medical device against emergent ionizing radiation injury.

Case Report: A Pregnant Woman Diagnosed as ALK-Rearrangement Lung Large Cell Neuroendocrine Cancer With Brain Metastasis.

Concomitant malignant tumors and pregnancy present many difficult questions to both clinicians and patients. Due to no specific guidelines, each aspect of clinical management requires special considerations. This current report presents a rare case of a 38-year-old pregnant woman at gestational age 33 weeks with complaints of weakness of her right limbs for 2 weeks. After successive cesarean section and craniotomy, a diagnosis of lung large cell neuroendocrine carcinoma (LCNEC) metastatic to the brain was eventually made. Next generation sequencing (NGS) showed ALK-EML4 gene fusion. Immediately afterwards she was started on the targeted therapy with the ALK inhibitor alectinib. Ten months later, all known lesions exhibited a rapid regression, and no new brain metastases were found. Consequently, the therapeutic effect was considered as a partial response. Then, we review the previous literature using PubMed on maternal malignant brain tumors diagnosed during pregnancy, or lung LCNEC associated with ALK fusion, or ALK inhibitors treatment among the pregnant women, eventually, and discuss the concerns of dealing with these patients.

Ferroptosis: A New Strategy for Cancer Therapy.

Ferroptosis is a newly discovered form of iron-dependent cell death, which is different from other death forms. The main characteristics of ferroptosis are: (1) Amino acid metabolism. (2) Iron metabolism; (3) Lipid metabolism and Reactive oxygen species (ROS). Ferroptosis is related to the occurrence and development of a variety of cancers, especially in the drug resistance. This article reviews the research progress of iron death in tumors, and provides a theoretical reference for its further research and clinical application.

Catheterization of Ventral Caudal Artery in Rats: A Modified Technique for Repeatable Angiography and Intervention.

BACKGROUND: The use of digital silhouette angiography (DSA) has been restricted due to lack of a technique that allows for repeated intra-arterial inspections over a prolonged period. Current studies are focused on the arteries that can be cannulated multiple times. We intended to develop and test a technique that would enable repeated performance of various catheterizations and transcatheter operations for a prolonged period, at the same site, with fewer postsurgical complications. METHODS: Thirty rats were randomly divided into five groups. Ventral caudal artery cannulation was performed via the transtail approach after grouping for subsequent experiments. Histological staining and scanning electron microscopy were used to assess endothelial injuries. RESULTS: The rats survived post catheterization of ventral caudal artery and establishment of animal models. The average time of ventral caudal artery cannulation was significantly shorter than that of the femoral (p < 0.01) and common carotid arteries (p < 0.01). In rats, the transtail artery technique effectively allowed selective arterial catheterization and angiography. Histological staining and scanning electron microscopy of the abdominal aorta revealed disruption of the intima and denuded wavy endothelial surface. CONCLUSIONS: We describe a novel method for artery sheath catheterization through the ventral caudal artery in rats; it may be possible to perform serial DSA studies and interventional operations with a single sheath channel in rats over a prolonged period. We believe that this approach will improve the utility of rats as models of human diseases and enable the broader use of rodent models for endovascular therapy research.

Melatonin modulates metabolic remodeling in HNSCC by suppressing MTHFD1L-formate axis.

Metabolic remodeling is now widely recognized as a hallmark of cancer, yet its role in head and neck squamous cell carcinoma (HNSCC) remains largely unknown. In this study, metabolomic analysis of melatonin-treated HNSCC cell lines revealed that exogenous melatonin inhibited many important metabolic pathways including folate cycle in HNSCC cells. Methylenetetrahydrofolate dehydrogenase 1 like (MTHFD1L), a metabolic enzyme of the folate cycle regulating the production of formate, was identified as a downstream target of melatonin. MTHFD1L was found to be markedly upregulated in HNSCC, and MTHFD1L overexpression was significantly associated with unfavorable clinical outcome of HNSCC patients. In addition, MTHFD1L promoted HNSCC progression in vitro and in vivo and reversed the oncostatic effects of exogenous melatonin. More importantly, the malignant phenotypes suppressed by knockdown of MTHFD1L or exogenous melatonin could be partially rescued by formate. Furthermore, we found that melatonin inhibited the expression of MTHFD1L in HNSCC cells through the downregulation of cyclic AMP-responsive element-binding protein 1 (CREB1) phosphorylation. Lastly, this novel regulatory axis of melatonin-p-CREB1-MTHFD1L-formate was also verified in HNSCC tissues. Collectively, our findings have demonstrated that MTHFD1L-formate axis promotes HNSCC progression and melatonin inhibits HNSCC progression through CREB1-mediated downregulation of MTHFD1L and formate. These findings have revealed new metabolic mechanisms in HNSCC and may provide novel insights on the therapeutic intervention of HNSCC.

Implantable platinum nanotree microelectrode with a battery-free electrochemical patch for peritoneal carcinomatosis monitoring.

As a severe stage of cancers, peritoneal carcinomatosis should be frequently monitored by means of ascites analysis. Nevertheless, the analysis process is traumatic and time-consuming in clinical practice. In this study, an implantable platinum nanotree microelectrode with a wireless, battery-free and flexible electrochemical patch was developed for in vivo and real-time peritoneal glucose detection to monitor peritoneal carcinomatosis. As the core of implantable microelectrode, platinum trees were synthesized by one-step electrodeposition method and highly sensitive to glucose detection. The platinum nanotree microelectrode was implantable in peritoneal cavity in minimally invasive way. A flexible circuit patch could execute electrochemical test and realize wireless power harvesting and data interaction with a near field communication (NFC)-enabled smartphone. The whole system could detect glucose dynamics in vivo in rat peritoneal cavity. Furthermore, the accuracy of this system was validated in ascites of patients. In this way, the system could offer hassle-free, rapid and minimally invasive opportunities toward peritoneal carcinomatosis monitoring.